                         SEQUENCE LISTING

<110>  Horizon Discovery Limited
       Dharmacon, Inc.
 
<120>  Method for producing genetically modified cells

<130>  P33736WO1

<150>  US 06/133942
<151>  2021-01-05

<150>  US 06/133945
<151>  2021-01-05

<150>  US 06/133948
<151>  2021-01-05

<160>  73    

<170>  PatentIn version 3.5

<210>  1
<211>  42
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Type II crRNA seq


<220>
<221>  misc_feature
<222>  (1)..(20)
<223>  n is a, c, g, or u

<400>  1
nnnnnnnnnn nnnnnnnnnn guuuuagagc uaugcuguuu ug                          42


<210>  2
<211>  99
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Type II tracrRNA seq

<400>  2
aacagcauag caaguuaaaa uaaggcuagu ccguuaucaa cuugaaaaag uggcaccgag       60

ucggugcgcg cacaugagga ucacccaugu gcuuuuuuu                              99


<210>  3
<211>  44
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AsCas12a crRNA Targets PPIB seq

<400>  3
uaauuucuac ucuuguagau acctacgaat tggagatgaa gatg                        44


<210>  4
<211>  158
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AaCas12b sgRNA - Targets PPIB seq

<400>  4
ggtctaaagg acagaatttt tcaacgggtg tgccaatggc cactttccag gtggcaaagc       60

ccgttgaact tctcaaaaag aacgctcgct cagtgttctg acgtcggatc actgagcgag      120

cgatctgaga agtggcacac ctacgaattg gagatgaa                              158


<210>  5
<211>  70
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Cas12d15 scoutRNA seq

<400>  5
cuuaguuaag gauguuccag guucuuucgg gagccuuggc cuucucccuu aaccuaugcc       60

acuaaugauu                                                              70


<210>  6
<211>  45
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cas12d15 crRNA - Targets PPIB seq

<400>  6
acccguaaag cagagcgaug aaggcaccta cgaattggag atgaa                       45


<210>  7
<211>  66
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Telomerase Ku binding motif / Ku heterodimer - Ku binding hairpin
       seq

<400>  7
uucuugucgu acuuauagau cgcuacguua uuucaauuuu gaaaaucuga guccugggag       60

ugcgga                                                                  66


<210>  8
<211>  1094
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Telomerase Ku binding motif / Ku heterodimer - Ku heterodimer seq

<400>  8

Met Ser Gly Trp Glu Ser Tyr Tyr Lys Thr Glu Gly Asp Glu Glu Ala 
1               5                   10                  15      


Glu Glu Glu Gln Glu Glu Asn Leu Glu Ala Ser Gly Asp Tyr Lys Tyr 
            20                  25                  30          


Ser Gly Arg Asp Ser Leu Ile Phe Leu Val Asp Ala Ser Lys Ala Met 
        35                  40                  45              


Phe Glu Ser Gln Ser Glu Asp Glu Leu Thr Pro Phe Asp Met Ser Ile 
    50                  55                  60                  


Gln Cys Ile Gln Ser Val Tyr Ile Ser Lys Ile Ile Ser Ser Asp Arg 
65                  70                  75                  80  


Asp Leu Leu Ala Val Val Phe Tyr Gly Thr Glu Lys Asp Lys Asn Ser 
                85                  90                  95      


Val Asn Phe Lys Asn Ile Tyr Val Leu Gln Glu Leu Asp Asn Pro Gly 
            100                 105                 110         


Ala Lys Arg Ile Leu Glu Leu Asp Gln Phe Lys Gly Gln Gln Gly Gln 
        115                 120                 125             


Lys Arg Phe Gln Asp Met Met Gly His Gly Ser Asp Tyr Ser Leu Ser 
    130                 135                 140                 


Glu Val Leu Trp Val Cys Ala Asn Leu Phe Ser Asp Val Gln Phe Lys 
145                 150                 155                 160 


Met Ser His Lys Arg Ile Met Leu Phe Thr Asn Glu Asp Asn Pro His 
                165                 170                 175     


Gly Asn Asp Ser Ala Lys Ala Ser Arg Ala Arg Thr Lys Ala Gly Asp 
            180                 185                 190         


Leu Arg Asp Thr Gly Ile Phe Leu Asp Leu Met His Leu Lys Lys Pro 
        195                 200                 205             


Gly Gly Phe Asp Ile Ser Leu Phe Tyr Arg Asp Ile Ile Ser Ile Ala 
    210                 215                 220                 


Glu Asp Glu Asp Leu Arg Val His Phe Glu Glu Ser Ser Lys Leu Glu 
225                 230                 235                 240 


Asp Leu Leu Arg Lys Val Arg Ala Lys Glu Thr Arg Lys Arg Ala Leu 
                245                 250                 255     


Ser Arg Leu Lys Leu Lys Leu Asn Lys Asp Ile Val Ile Ser Val Gly 
            260                 265                 270         


Ile Tyr Asn Leu Val Gln Lys Ala Leu Lys Pro Pro Pro Ile Lys Leu 
        275                 280                 285             


Tyr Arg Glu Thr Asn Glu Pro Val Lys Thr Lys Thr Arg Thr Phe Asn 
    290                 295                 300                 


Thr Ser Thr Gly Gly Leu Leu Leu Pro Ser Asp Thr Lys Arg Ser Gln 
305                 310                 315                 320 


Ile Tyr Gly Ser Arg Gln Ile Ile Leu Glu Lys Glu Glu Thr Glu Glu 
                325                 330                 335     


Leu Lys Arg Phe Asp Asp Pro Gly Leu Met Leu Met Gly Phe Lys Pro 
            340                 345                 350         


Leu Val Leu Leu Lys Lys His His Tyr Leu Arg Pro Ser Leu Phe Val 
        355                 360                 365             


Tyr Pro Glu Glu Ser Leu Val Ile Gly Ser Ser Thr Leu Phe Ser Ala 
    370                 375                 380                 


Leu Leu Ile Lys Cys Leu Glu Lys Glu Val Ala Ala Leu Cys Arg Tyr 
385                 390                 395                 400 


Thr Pro Arg Arg Asn Ile Pro Pro Tyr Phe Val Ala Leu Val Pro Gln 
                405                 410                 415     


Glu Glu Glu Leu Asp Asp Gln Lys Ile Gln Val Thr Pro Pro Gly Phe 
            420                 425                 430         


Gln Leu Val Phe Leu Pro Phe Ala Asp Asp Lys Arg Lys Met Pro Phe 
        435                 440                 445             


Thr Glu Lys Ile Met Ala Thr Pro Glu Gln Val Gly Lys Met Lys Ala 
    450                 455                 460                 


Ile Val Glu Lys Leu Arg Phe Thr Tyr Arg Ser Asp Ser Phe Glu Asn 
465                 470                 475                 480 


Pro Val Leu Gln Gln His Phe Arg Asn Leu Glu Ala Leu Ala Leu Asp 
                485                 490                 495     


Leu Met Glu Pro Glu Gln Ala Val Asp Leu Thr Leu Pro Lys Val Glu 
            500                 505                 510         


Ala Met Asn Lys Arg Leu Gly Ser Leu Val Asp Glu Phe Lys Glu Leu 
        515                 520                 525             


Val Tyr Pro Pro Asp Tyr Asn Pro Glu Gly Lys Val Thr Lys Arg Lys 
    530                 535                 540                 


His Asp Asn Glu Gly Ser Gly Ser Lys Arg Pro Lys Val Glu Tyr Ser 
545                 550                 555                 560 


Glu Glu Glu Leu Lys Thr His Ile Ser Lys Gly Thr Leu Gly Lys Phe 
                565                 570                 575     


Thr Val Pro Met Leu Lys Glu Ala Cys Arg Ala Tyr Gly Leu Lys Ser 
            580                 585                 590         


Gly Leu Lys Lys Gln Glu Leu Leu Glu Ala Leu Thr Lys His Phe Gln 
        595                 600                 605             


Asp Met Val Arg Ser Gly Asn Lys Ala Ala Val Val Leu Cys Met Asp 
    610                 615                 620                 


Val Gly Phe Thr Met Ser Asn Ser Ile Pro Gly Ile Glu Ser Pro Phe 
625                 630                 635                 640 


Glu Gln Ala Lys Lys Val Ile Thr Met Phe Val Gln Arg Gln Val Phe 
                645                 650                 655     


Ala Glu Asn Lys Asp Glu Ile Ala Leu Val Leu Phe Gly Thr Asp Gly 
            660                 665                 670         


Thr Asp Asn Pro Leu Ser Gly Gly Asp Gln Tyr Gln Asn Ile Thr Val 
        675                 680                 685             


His Arg His Leu Met Leu Pro Asp Phe Asp Leu Leu Glu Asp Ile Glu 
    690                 695                 700                 


Ser Lys Ile Gln Pro Gly Ser Gln Gln Ala Asp Phe Leu Asp Ala Leu 
705                 710                 715                 720 


Ile Val Ser Met Asp Val Ile Gln His Glu Thr Ile Gly Lys Lys Phe 
                725                 730                 735     


Glu Lys Arg His Ile Glu Ile Phe Thr Asp Leu Ser Ser Arg Phe Ser 
            740                 745                 750         


Lys Ser Gln Leu Asp Ile Ile Ile His Ser Leu Lys Lys Cys Asp Ile 
        755                 760                 765             


Ser Glu Arg His Ser Ile His Trp Pro Cys Arg Leu Thr Ile Gly Ser 
    770                 775                 780                 


Asn Leu Ser Ile Arg Ile Ala Ala Tyr Lys Ser Ile Leu Gln Glu Arg 
785                 790                 795                 800 


Val Lys Lys Thr Trp Thr Val Val Asp Ala Lys Thr Leu Lys Lys Glu 
                805                 810                 815     


Asp Ile Gln Lys Glu Thr Val Tyr Cys Leu Asn Asp Asp Asp Glu Thr 
            820                 825                 830         


Glu Val Leu Lys Glu Asp Ile Ile Gln Gly Phe Arg Tyr Gly Ser Asp 
        835                 840                 845             


Ile Val Pro Phe Ser Lys Val Asp Glu Glu Gln Met Lys Tyr Lys Ser 
    850                 855                 860                 


Glu Gly Lys Cys Phe Ser Val Leu Gly Phe Cys Lys Ser Ser Gln Val 
865                 870                 875                 880 


Gln Arg Arg Phe Phe Met Gly Asn Gln Val Leu Lys Val Phe Ala Ala 
                885                 890                 895     


Arg Asp Asp Glu Ala Ala Ala Val Ala Leu Ser Ser Leu Ile His Ala 
            900                 905                 910         


Leu Asp Asp Leu Asp Met Val Ala Ile Val Arg Tyr Ala Tyr Asp Lys 
        915                 920                 925             


Arg Ala Asn Pro Gln Val Gly Val Ala Phe Pro His Ile Lys His Asn 
    930                 935                 940                 


Tyr Glu Cys Leu Val Tyr Val Gln Leu Pro Phe Met Glu Asp Leu Arg 
945                 950                 955                 960 


Gln Tyr Met Phe Ser Ser Leu Lys Asn Ser Lys Lys Tyr Ala Pro Thr 
                965                 970                 975     


Glu Ala Gln Leu Asn Ala Val Asp Ala Leu Ile Asp Ser Met Ser Leu 
            980                 985                 990         


Ala Lys Lys Asp Glu Lys Thr Asp  Thr Leu Glu Asp Leu  Phe Pro Thr 
        995                 1000                 1005             


Thr Lys  Ile Pro Asn Pro Arg  Phe Gln Arg Leu Phe  Gln Cys Leu 
    1010                 1015                 1020             


Leu His  Arg Ala Leu His Pro  Arg Glu Pro Leu Pro  Pro Ile Gln 
    1025                 1030                 1035             


Gln His  Ile Trp Asn Met Leu  Asn Pro Pro Ala Glu  Val Thr Thr 
    1040                 1045                 1050             


Lys Ser  Gln Ile Pro Leu Ser  Lys Ile Lys Thr Leu  Phe Pro Leu 
    1055                 1060                 1065             


Ile Glu  Ala Lys Lys Lys Asp  Gln Val Thr Ala Gln  Glu Ile Phe 
    1070                 1075                 1080             


Gln Asp  Asn His Glu Asp Gly  Pro Thr Ala Lys 
    1085                 1090                 


<210>  9
<211>  10
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Telomerase Sm7 binding motif / Sm7 homoheptamer - Sm consensus 
       site seq

<400>  9
aauuuuugga                                                              10


<210>  10
<211>  83
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Telomerase Sm7 binding motif / Sm7 homoheptamer - Monomeric Sm - 
       like protein (archaea)

<400>  10

Gly Ser Val Ile Asp Val Ser Ser Gln Arg Val Asn Val Gln Arg Pro 
1               5                   10                  15      


Leu Asp Ala Leu Gly Asn Ser Leu Asn Ser Pro Val Ile Ile Lys Leu 
            20                  25                  30          


Lys Gly Asp Arg Glu Phe Arg Gly Val Leu Lys Ser Phe Asp Leu His 
        35                  40                  45              


Met Asn Leu Val Leu Asn Asp Ala Glu Glu Leu Glu Asp Gly Glu Val 
    50                  55                  60                  


Thr Arg Arg Leu Gly Thr Val Leu Ile Arg Gly Asp Asn Ile Val Tyr 
65                  70                  75                  80  


Ile Ser Pro 
            


<210>  11
<211>  25
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  MS2 phage operator stem loop / MS2 coat protein - MS2 phage 
       operator stem loop seq

<400>  11
gcgcacauga ggaucaccca ugugc                                             25


<210>  12
<211>  117
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  MS2 phage operator stem loop / MS2 coat protein - MS2 coat 
       protein

<400>  12

Met Ala Ser Asn Phe Thr Gln Phe Val Leu Val Asp Asn Gly Gly Thr 
1               5                   10                  15      


Gly Asp Val Thr Val Ala Pro Ser Asn Phe Ala Asn Gly Ile Ala Glu 
            20                  25                  30          


Trp Ile Ser Ser Asn Ser Arg Ser Gln Ala Tyr Lys Val Thr Cys Ser 
        35                  40                  45              


Val Arg Gln Ser Ser Ala Gln Asn Arg Lys Tyr Thr Ile Lys Val Glu 
    50                  55                  60                  


Val Pro Lys Gly Ala Trp Arg Ser Tyr Leu Asn Met Glu Leu Thr Ile 
65                  70                  75                  80  


Pro Ile Phe Ala Thr Asn Ser Asp Cys Glu Leu Ile Val Lys Ala Met 
                85                  90                  95      


Gln Gly Leu Leu Lys Asp Gly Asn Pro Ile Pro Ser Ala Ile Ala Ala 
            100                 105                 110         


Asn Ser Gly Ile Tyr 
        115         


<210>  13
<211>  25
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  PP7 phage operator stem loop / PP7 coat protein - PP7 phage 
       operator stem loop seq

<400>  13
auaaggaguu uauauggaaa cccuu                                             25


<210>  14
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PP7 phage operator stem loop / PP7 coat protein - PP7 coat 
       protein (PCP) seq

<400>  14

Met Ser Lys Thr Ile Val Leu Ser Val Gly Glu Ala Thr Arg Thr Leu 
1               5                   10                  15      


Thr Glu Ile Gln Ser Thr Ala Asp Arg Gln Ile Phe Glu Glu Lys Val 
            20                  25                  30          


Gly Pro Leu Val Gly Arg Leu Arg Leu Thr Ala Ser Leu Arg Gln Asn 
        35                  40                  45              


Gly Ala Lys Thr Ala Tyr Arg Val Asn Leu Lys Leu Asp Gln Ala Asp 
    50                  55                  60                  


Val Val Asp Cys Ser Thr Ser Val Cys Gly Glu Leu Pro Lys Val Arg 
65                  70                  75                  80  


Tyr Thr Gln Val Trp Ser His Asp Val Thr Ile Val Ala Asn Ser Thr 
                85                  90                  95      


Glu Ala Ser Arg Lys Ser Leu Tyr Asp Leu Thr Lys Ser Leu Val Ala 
            100                 105                 110         


Thr Ser Gln Val Glu Asp Leu Val Val Asn Leu Val Pro Leu Gly Arg 
        115                 120                 125             


<210>  15
<211>  19
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  SfMu Com stem loop / SfMu Com binding protein - SfMu Com stem 
       loop seq

<400>  15
cugaaugccu gcgagcauc                                                    19


<210>  16
<211>  62
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  SfMu Com stem loop / SfMu Com binding protein - SfMu Com binding 
       protein seq

<400>  16

Met Lys Ser Ile Arg Cys Lys Asn Cys Asn Lys Leu Leu Phe Lys Ala 
1               5                   10                  15      


Asp Ser Phe Asp His Ile Glu Ile Arg Cys Pro Arg Cys Lys Arg His 
            20                  25                  30          


Ile Ile Met Leu Asn Ala Cys Glu His Pro Thr Glu Lys His Cys Gly 
        35                  40                  45              


Lys Arg Glu Lys Ile Thr His Ser Asp Glu Thr Val Arg Tyr 
    50                  55                  60          


<210>  17
<211>  1368
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanised amino acid sequence Streptococcus pyogenes dCas9 seq

<400>  17

Met Asp Lys Lys Tyr Ser Ile Gly Leu Ala Ile Gly Thr Asn Ser Val 
1               5                   10                  15      


Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe 
            20                  25                  30          


Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile 
        35                  40                  45              


Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 
    50                  55                  60                  


Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 
65                  70                  75                  80  


Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 
                85                  90                  95      


Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 
            100                 105                 110         


His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 
        115                 120                 125             


His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp 
    130                 135                 140                 


Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 
145                 150                 155                 160 


Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro 
                165                 170                 175     


Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 
            180                 185                 190         


Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala 
        195                 200                 205             


Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 
    210                 215                 220                 


Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 
225                 230                 235                 240 


Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe 
                245                 250                 255     


Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 
            260                 265                 270         


Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 
        275                 280                 285             


Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp 
    290                 295                 300                 


Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 
305                 310                 315                 320 


Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 
                325                 330                 335     


Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 
            340                 345                 350         


Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 
        355                 360                 365             


Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 
    370                 375                 380                 


Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg 
385                 390                 395                 400 


Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu 
                405                 410                 415     


Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 
            420                 425                 430         


Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 
        435                 440                 445             


Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 
    450                 455                 460                 


Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 
465                 470                 475                 480 


Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 
                485                 490                 495     


Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 
            500                 505                 510         


Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 
        515                 520                 525             


Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 
    530                 535                 540                 


Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr 
545                 550                 555                 560 


Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 
                565                 570                 575     


Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 
            580                 585                 590         


Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 
        595                 600                 605             


Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 
    610                 615                 620                 


Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 
625                 630                 635                 640 


His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 
                645                 650                 655     


Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 
            660                 665                 670         


Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 
        675                 680                 685             


Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 
    690                 695                 700                 


Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu 
705                 710                 715                 720 


His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly 
                725                 730                 735     


Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly 
            740                 745                 750         


Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln 
        755                 760                 765             


Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile 
    770                 775                 780                 


Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro 
785                 790                 795                 800 


Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu 
                805                 810                 815     


Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg 
            820                 825                 830         


Leu Ser Asp Tyr Asp Val Asp Ala Ile Val Pro Gln Ser Phe Leu Lys 
        835                 840                 845             


Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg 
    850                 855                 860                 


Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys 
865                 870                 875                 880 


Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys 
                885                 890                 895     


Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp 
            900                 905                 910         


Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr 
        915                 920                 925             


Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp 
    930                 935                 940                 


Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser 
945                 950                 955                 960 


Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg 
                965                 970                 975     


Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val 
            980                 985                 990         


Val Gly Thr Ala Leu Ile Lys Lys  Tyr Pro Lys Leu Glu  Ser Glu Phe 
        995                 1000                 1005             


Val Tyr  Gly Asp Tyr Lys Val  Tyr Asp Val Arg Lys  Met Ile Ala 
    1010                 1015                 1020             


Lys Ser  Glu Gln Glu Ile Gly  Lys Ala Thr Ala Lys  Tyr Phe Phe 
    1025                 1030                 1035             


Tyr Ser  Asn Ile Met Asn Phe  Phe Lys Thr Glu Ile  Thr Leu Ala 
    1040                 1045                 1050             


Asn Gly  Glu Ile Arg Lys Arg  Pro Leu Ile Glu Thr  Asn Gly Glu 
    1055                 1060                 1065             


Thr Gly  Glu Ile Val Trp Asp  Lys Gly Arg Asp Phe  Ala Thr Val 
    1070                 1075                 1080             


Arg Lys  Val Leu Ser Met Pro  Gln Val Asn Ile Val  Lys Lys Thr 
    1085                 1090                 1095             


Glu Val  Gln Thr Gly Gly Phe  Ser Lys Glu Ser Ile  Leu Pro Lys 
    1100                 1105                 1110             


Arg Asn  Ser Asp Lys Leu Ile  Ala Arg Lys Lys Asp  Trp Asp Pro 
    1115                 1120                 1125             


Lys Lys  Tyr Gly Gly Phe Asp  Ser Pro Thr Val Ala  Tyr Ser Val 
    1130                 1135                 1140             


Leu Val  Val Ala Lys Val Glu  Lys Gly Lys Ser Lys  Lys Leu Lys 
    1145                 1150                 1155             


Ser Val  Lys Glu Leu Leu Gly  Ile Thr Ile Met Glu  Arg Ser Ser 
    1160                 1165                 1170             


Phe Glu  Lys Asn Pro Ile Asp  Phe Leu Glu Ala Lys  Gly Tyr Lys 
    1175                 1180                 1185             


Glu Val  Lys Lys Asp Leu Ile  Ile Lys Leu Pro Lys  Tyr Ser Leu 
    1190                 1195                 1200             


Phe Glu  Leu Glu Asn Gly Arg  Lys Arg Met Leu Ala  Ser Ala Gly 
    1205                 1210                 1215             


Glu Leu  Gln Lys Gly Asn Glu  Leu Ala Leu Pro Ser  Lys Tyr Val 
    1220                 1225                 1230             


Asn Phe  Leu Tyr Leu Ala Ser  His Tyr Glu Lys Leu  Lys Gly Ser 
    1235                 1240                 1245             


Pro Glu  Asp Asn Glu Gln Lys  Gln Leu Phe Val Glu  Gln His Lys 
    1250                 1255                 1260             


His Tyr  Leu Asp Glu Ile Ile  Glu Gln Ile Ser Glu  Phe Ser Lys 
    1265                 1270                 1275             


Arg Val  Ile Leu Ala Asp Ala  Asn Leu Asp Lys Val  Leu Ser Ala 
    1280                 1285                 1290             


Tyr Asn  Lys His Arg Asp Lys  Pro Ile Arg Glu Gln  Ala Glu Asn 
    1295                 1300                 1305             


Ile Ile  His Leu Phe Thr Leu  Thr Asn Leu Gly Ala  Pro Ala Ala 
    1310                 1315                 1320             


Phe Lys  Tyr Phe Asp Thr Thr  Ile Asp Arg Lys Arg  Tyr Thr Ser 
    1325                 1330                 1335             


Thr Lys  Glu Val Leu Asp Ala  Thr Leu Ile His Gln  Ser Ile Thr 
    1340                 1345                 1350             


Gly Leu  Tyr Glu Thr Arg Ile  Asp Leu Ser Gln Leu  Gly Gly Asp 
    1355                 1360                 1365             


<210>  18
<211>  1367
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cas9 D10A Amino Acid Sequence

<400>  18

Asp Lys Lys Tyr Ser Ile Gly Leu Ala Ile Gly Thr Asn Ser Val Gly 
1               5                   10                  15      


Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe Lys 
            20                  25                  30          


Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile Gly 
        35                  40                  45              


Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu Lys 
    50                  55                  60                  


Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys Tyr 
65                  70                  75                  80  


Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser Phe 
                85                  90                  95      


Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys His 
            100                 105                 110         


Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr His 
        115                 120                 125             


Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp Ser 
    130                 135                 140                 


Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His Met 
145                 150                 155                 160 


Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro Asp 
                165                 170                 175     


Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr Asn 
            180                 185                 190         


Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala Lys 
        195                 200                 205             


Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn Leu 
    210                 215                 220                 


Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn Leu 
225                 230                 235                 240 


Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe Asp 
                245                 250                 255     


Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp Asp 
            260                 265                 270         


Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp Leu 
        275                 280                 285             


Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp Ile 
    290                 295                 300                 


Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser Met 
305                 310                 315                 320 


Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys Ala 
                325                 330                 335     


Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe Asp 
            340                 345                 350         


Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser Gln 
        355                 360                 365             


Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp Gly 
    370                 375                 380                 


Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg Lys 
385                 390                 395                 400 


Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu Gly 
                405                 410                 415     


Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe Leu 
            420                 425                 430         


Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile Pro 
        435                 440                 445             


Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp Met 
    450                 455                 460                 


Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu Val 
465                 470                 475                 480 


Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr Asn 
                485                 490                 495     


Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser Leu 
            500                 505                 510         


Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys Tyr 
        515                 520                 525             


Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln Lys 
    530                 535                 540                 


Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr Val 
545                 550                 555                 560 


Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp Ser 
                565                 570                 575     


Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly Thr 
            580                 585                 590         


Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp Asn 
        595                 600                 605             


Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr Leu 
    610                 615                 620                 


Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala His 
625                 630                 635                 640 


Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr Thr 
                645                 650                 655     


Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp Lys 
            660                 665                 670         


Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe Ala 
        675                 680                 685             


Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe Lys 
    690                 695                 700                 


Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu His 
705                 710                 715                 720 


Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly Ile 
                725                 730                 735     


Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly Arg 
            740                 745                 750         


His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln Thr 
        755                 760                 765             


Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile Glu 
    770                 775                 780                 


Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro Val 
785                 790                 795                 800 


Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu Gln 
                805                 810                 815     


Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg Leu 
            820                 825                 830         


Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys Asp 
        835                 840                 845             


Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg Gly 
    850                 855                 860                 


Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys Asn 
865                 870                 875                 880 


Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe 
                885                 890                 895     


Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys 
            900                 905                 910         


Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys 
        915                 920                 925             


His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp Glu 
    930                 935                 940                 


Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser Lys 
945                 950                 955                 960 


Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg Glu 
                965                 970                 975     


Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val Val 
            980                 985                 990         


Gly Thr Ala Leu Ile Lys Lys Tyr  Pro Lys Leu Glu Ser  Glu Phe Val 
        995                 1000                 1005             


Tyr Gly  Asp Tyr Lys Val Tyr  Asp Val Arg Lys Met  Ile Ala Lys 
    1010                 1015                 1020             


Ser Glu  Gln Glu Ile Gly Lys  Ala Thr Ala Lys Tyr  Phe Phe Tyr 
    1025                 1030                 1035             


Ser Asn  Ile Met Asn Phe Phe  Lys Thr Glu Ile Thr  Leu Ala Asn 
    1040                 1045                 1050             


Gly Glu  Ile Arg Lys Arg Pro  Leu Ile Glu Thr Asn  Gly Glu Thr 
    1055                 1060                 1065             


Gly Glu  Ile Val Trp Asp Lys  Gly Arg Asp Phe Ala  Thr Val Arg 
    1070                 1075                 1080             


Lys Val  Leu Ser Met Pro Gln  Val Asn Ile Val Lys  Lys Thr Glu 
    1085                 1090                 1095             


Val Gln  Thr Gly Gly Phe Ser  Lys Glu Ser Ile Leu  Pro Lys Arg 
    1100                 1105                 1110             


Asn Ser  Asp Lys Leu Ile Ala  Arg Lys Lys Asp Trp  Asp Pro Lys 
    1115                 1120                 1125             


Lys Tyr  Gly Gly Phe Asp Ser  Pro Thr Val Ala Tyr  Ser Val Leu 
    1130                 1135                 1140             


Val Val  Ala Lys Val Glu Lys  Gly Lys Ser Lys Lys  Leu Lys Ser 
    1145                 1150                 1155             


Val Lys  Glu Leu Leu Gly Ile  Thr Ile Met Glu Arg  Ser Ser Phe 
    1160                 1165                 1170             


Glu Lys  Asn Pro Ile Asp Phe  Leu Glu Ala Lys Gly  Tyr Lys Glu 
    1175                 1180                 1185             


Val Lys  Lys Asp Leu Ile Ile  Lys Leu Pro Lys Tyr  Ser Leu Phe 
    1190                 1195                 1200             


Glu Leu  Glu Asn Gly Arg Lys  Arg Met Leu Ala Ser  Ala Gly Glu 
    1205                 1210                 1215             


Leu Gln  Lys Gly Asn Glu Leu  Ala Leu Pro Ser Lys  Tyr Val Asn 
    1220                 1225                 1230             


Phe Leu  Tyr Leu Ala Ser His  Tyr Glu Lys Leu Lys  Gly Ser Pro 
    1235                 1240                 1245             


Glu Asp  Asn Glu Gln Lys Gln  Leu Phe Val Glu Gln  His Lys His 
    1250                 1255                 1260             


Tyr Leu  Asp Glu Ile Ile Glu  Gln Ile Ser Glu Phe  Ser Lys Arg 
    1265                 1270                 1275             


Val Ile  Leu Ala Asp Ala Asn  Leu Asp Lys Val Leu  Ser Ala Tyr 
    1280                 1285                 1290             


Asn Lys  His Arg Asp Lys Pro  Ile Arg Glu Gln Ala  Glu Asn Ile 
    1295                 1300                 1305             


Ile His  Leu Phe Thr Leu Thr  Asn Leu Gly Ala Pro  Ala Ala Phe 
    1310                 1315                 1320             


Lys Tyr  Phe Asp Thr Thr Ile  Asp Arg Lys Arg Tyr  Thr Ser Thr 
    1325                 1330                 1335             


Lys Glu  Val Leu Asp Ala Thr  Leu Ile His Gln Ser  Ile Thr Gly 
    1340                 1345                 1350             


Leu Tyr  Glu Thr Arg Ile Asp  Leu Ser Gln Leu Gly  Gly Asp 
    1355                 1360                 1365         


<210>  19
<211>  4101
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cas9 D10A Protein Nucleotide Sequence

<400>  19
gataaaaagt attctattgg tttagccatc ggcactaatt ccgttggatg ggctgtcata       60

accgatgaat acaaagtacc ttcaaagaaa tttaaggtgt tggggaacac agaccgtcat      120

tcgattaaaa agaatcttat cggtgccctc ctattcgata gtggcgaaac ggcagaggcg      180

actcgcctga aacgaaccgc tcggagaagg tatacacgtc gcaagaaccg aatatgttac      240

ttacaagaaa tttttagcaa tgagatggcc aaagttgacg attctttctt tcaccgtttg      300

gaagagtcct tccttgtcga agaggacaag aaacatgaac ggcaccccat ctttggaaac      360

atagtagatg aggtggcata tcatgaaaag tacccaacga tttatcacct cagaaaaaag      420

ctagttgact caactgataa agcggacctg aggttaatct acttggctct tgcccatatg      480

ataaagttcc gtgggcactt tctcattgag ggtgatctaa atccggacaa ctcggatgtc      540

gacaaactgt tcatccagtt agtacaaacc tataatcagt tgtttgaaga gaaccctata      600

aatgcaagtg gcgtggatgc gaaggctatt cttagcgccc gcctctctaa atcccgacgg      660

ctagaaaacc tgatcgcaca attacccgga gagaagaaaa atgggttgtt cggtaacctt      720

atagcgctct cactaggcct gacaccaaat tttaagtcga acttcgactt agctgaagat      780

gccaaattgc agcttagtaa ggacacgtac gatgacgatc tcgacaatct actggcacaa      840

attggagatc agtatgcgga cttatttttg gctgccaaaa accttagcga tgcaatcctc      900

ctatctgaca tactgagagt taatactgag attaccaagg cgccgttatc cgcttcaatg      960

atcaaaaggt acgatgaaca tcaccaagac ttgacacttc tcaaggccct agtccgtcag     1020

caactgcctg agaaatataa ggaaatattc tttgatcagt cgaaaaacgg gtacgcaggt     1080

tatattgacg gcggagcgag tcaagaggaa ttctacaagt ttatcaaacc catattagag     1140

aagatggatg ggacggaaga gttgcttgta aaactcaatc gcgaagatct actgcgaaag     1200

cagcggactt tcgacaacgg tagcattcca catcaaatcc acttaggcga attgcatgct     1260

atacttagaa ggcaggagga tttttatccg ttcctcaaag acaatcgtga aaagattgag     1320

aaaatcctaa cctttcgcat accttactat gtgggacccc tggcccgagg gaactctcgg     1380

ttcgcatgga tgacaagaaa gtccgaagaa acgattactc catggaattt tgaggaagtt     1440

gtcgataaag gtgcgtcagc tcaatcgttc atcgagagga tgaccaactt tgacaagaat     1500

ttaccgaacg aaaaagtatt gcctaagcac agtttacttt acgagtattt cacagtgtac     1560

aatgaactca cgaaagttaa gtatgtcact gagggcatgc gtaaacccgc ctttctaagc     1620

ggagaacaga agaaagcaat agtagatctg ttattcaaga ccaaccgcaa agtgacagtt     1680

aagcaattga aagaggacta ctttaagaaa attgaatgct tcgattctgt cgagatctcc     1740

ggggtagaag atcgatttaa tgcgtcactt ggtacgtatc atgacctcct aaagataatt     1800

aaagataagg acttcctgga taacgaagag aatgaagata tcttagaaga tatagtgttg     1860

actcttaccc tctttgaaga tcgggaaatg attgaggaaa gactaaaaac atacgctcac     1920

ctgttcgacg ataaggttat gaaacagtta aagaggcgtc gctatacggg ctggggacga     1980

ttgtcgcgga aacttatcaa cgggataaga gacaagcaaa gtggtaaaac tattctcgat     2040

tttctaaaga gcgacggctt cgccaatagg aactttatgc agctgatcca tgatgactct     2100

ttaaccttca aagaggatat acaaaaggca caggtttccg gacaagggga ctcattgcac     2160

gaacatattg cgaatcttgc tggttcgcca gccatcaaaa agggcatact ccagacagtc     2220

aaagtagtgg atgagctagt taaggtcatg ggacgtcaca aaccggaaaa cattgtaatc     2280

gagatggcac gcgaaaatca aacgactcag aaggggcaaa aaaacagtcg agagcggatg     2340

aagagaatag aagagggtat taaagaactg ggcagccaga tcttaaagga gcatcctgtg     2400

gaaaataccc aattgcagaa cgagaaactt tacctctatt acctacaaaa tggaagggac     2460

atgtatgttg atcaggaact ggacataaac cgtttatctg attacgacgt cgatcacatt     2520

gtaccccaat cctttttgaa ggacgattca atcgacaata aagtgcttac acgctcggat     2580

aagaaccgag ggaaaagtga caatgttcca agcgaggaag tcgtaaagaa aatgaagaac     2640

tattggcggc agctcctaaa tgcgaaactg ataacgcaaa gaaagttcga taacttaact     2700

aaagctgaga ggggtggctt gtctgaactt gacaaggccg gatttattaa acgtcagctc     2760

gtggaaaccc gccaaatcac aaagcatgtt gcacagatac tagattcccg aatgaatacg     2820

aaatacgacg agaacgataa gctgattcgg gaagtcaaag taatcacttt aaagtcaaaa     2880

ttggtgtcgg acttcagaaa ggattttcaa ttctataaag ttagggagat aaataactac     2940

caccatgcgc acgacgctta tcttaatgcc gtcgtaggga ccgcactcat taagaaatac     3000

ccgaagctag aaagtgagtt tgtgtatggt gattacaaag tttatgacgt ccgtaagatg     3060

atcgcgaaaa gcgaacagga gataggcaag gctacagcca aatacttctt ttattctaac     3120

attatgaatt tctttaagac ggaaatcact ctggcaaacg gagagatacg caaacgacct     3180

ttaattgaaa ccaatgggga gacaggtgaa atcgtatggg ataagggccg ggacttcgcg     3240

acggtgagaa aagttttgtc catgccccaa gtcaacatag taaagaaaac tgaggtgcag     3300

accggagggt tttcaaagga atcgattctt ccaaaaagga atagtgataa gctcatcgct     3360

cgtaaaaagg actgggaccc gaaaaagtac ggtggcttcg atagccctac agttgcctat     3420

tctgtcctag tagtggcaaa agttgagaag ggaaaatcca agaaactgaa gtcagtcaaa     3480

gaattattgg ggataacgat tatggagcgc tcgtcttttg aaaagaaccc catcgacttc     3540

cttgaggcga aaggttacaa ggaagtaaaa aaggatctca taattaaact accaaagtat     3600

agtctgtttg agttagaaaa tggccgaaaa cggatgttgg ctagcgccgg agagcttcaa     3660

aaggggaacg aactcgcact accgtctaaa tacgtgaatt tcctgtattt agcgtcccat     3720

tacgagaagt tgaaaggttc acctgaagat aacgaacaga agcaactttt tgttgagcag     3780

cacaaacatt atctcgacga aatcatagag caaatttcgg aattcagtaa gagagtcatc     3840

ctagctgatg ccaatctgga caaagtatta agcgcataca acaagcacag ggataaaccc     3900

atacgtgagc aggcggaaaa tattatccat ttgtttactc ttaccaacct cggcgctcca     3960

gccgcattca agtattttga cacaacgata gatcgcaaac gatacacttc taccaaggag     4020

gtgctagacg cgacactgat tcaccaatcc atcacgggat tatatgaaac tcggatagat     4080

ttgtcacagc ttgggggtga c                                               4101


<210>  20
<211>  128
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RNA scaffold expression cassette (S. pyogenes), containing a 
       20-nucleotide programmable sequence, a CRISPR RNA motif, and an 
       MS2 aptamer motif seq


<220>
<221>  misc_feature
<222>  (1)..(20)
<223>  n is a, c, g, or t

<400>  20
nnnnnnnnnn nnnnnnnnnn gttttagagc tagaaatagc aagttaaaat aaggctagtc       60

cgttatcaac ttgaaaaagt ggcaccgagt cggtgcgcgc acatgaggat cacccatgtg      120

cttttttt                                                               128


<210>  21
<211>  150
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RNA scaffold containing two MS2 loops seq

<400>  21
gttttagagc tagaaatagc aagttaaaat aaggctagtc cgttatcaac ttgaaaaagt       60

ggcaccgagt cggtgcggga gcacatgagg atcacccatg tgccacgagc gacatgagga      120

tcacccatgt cgctcgtgtt cccttttttt                                       150


<210>  22
<211>  340
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Effector AID-MCP fusion

<400>  22

Met Asp Ser Leu Leu Met Asn Arg Arg Lys Phe Leu Tyr Gln Phe Lys 
1               5                   10                  15      


Asn Val Arg Trp Ala Lys Gly Arg Arg Glu Thr Tyr Leu Cys Tyr Val 
            20                  25                  30          


Val Lys Arg Arg Asp Ser Ala Thr Ser Phe Ser Leu Asp Phe Gly Tyr 
        35                  40                  45              


Leu Arg Asn Lys Asn Gly Cys His Val Glu Leu Leu Phe Leu Arg Tyr 
    50                  55                  60                  


Ile Ser Asp Trp Asp Leu Asp Pro Gly Arg Cys Tyr Arg Val Thr Trp 
65                  70                  75                  80  


Phe Thr Ser Trp Ser Pro Cys Tyr Asp Cys Ala Arg His Val Ala Asp 
                85                  90                  95      


Phe Leu Arg Gly Asn Pro Asn Leu Ser Leu Arg Ile Phe Thr Ala Arg 
            100                 105                 110         


Leu Tyr Phe Cys Glu Asp Arg Lys Ala Glu Pro Glu Gly Leu Arg Arg 
        115                 120                 125             


Leu His Arg Ala Gly Val Gln Ile Ala Ile Met Thr Phe Lys Asp Tyr 
    130                 135                 140                 


Phe Tyr Cys Trp Asn Thr Phe Val Glu Asn His Glu Arg Thr Phe Lys 
145                 150                 155                 160 


Ala Trp Glu Gly Leu His Glu Asn Ser Val Arg Leu Ser Arg Gln Leu 
                165                 170                 175     


Arg Arg Ile Leu Leu Pro Leu Tyr Glu Val Asp Asp Leu Arg Asp Ala 
            180                 185                 190         


Phe Arg Thr Leu Gly Leu Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr 
        195                 200                 205             


His Thr Ser Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Met 
    210                 215                 220                 


Ala Ser Asn Phe Thr Gln Phe Val Leu Val Asp Asn Gly Gly Thr Gly 
225                 230                 235                 240 


Asp Val Thr Val Ala Pro Ser Asn Phe Ala Asn Gly Ile Ala Glu Trp 
                245                 250                 255     


Ile Ser Ser Asn Ser Arg Ser Gln Ala Tyr Lys Val Thr Cys Ser Val 
            260                 265                 270         


Arg Gln Ser Ser Ala Gln Asn Arg Lys Tyr Thr Ile Lys Val Glu Val 
        275                 280                 285             


Pro Lys Gly Ala Trp Arg Ser Tyr Leu Asn Met Glu Leu Thr Ile Pro 
    290                 295                 300                 


Ile Phe Ala Thr Asn Ser Asp Cys Glu Leu Ile Val Lys Ala Met Gln 
305                 310                 315                 320 


Gly Leu Leu Lys Asp Gly Asn Pro Ile Pro Ser Ala Ile Ala Ala Asn 
                325                 330                 335     


Ser Gly Ile Tyr 
            340 


<210>  23
<211>  594
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  wtAID cDNA seq

<400>  23
atggacagcc tcttgatgaa ccggaggaag tttctttacc aattcaaaaa tgtccgctgg       60

gctaagggtc ggcgtgagac ctacctgtgc tacgtagtga agaggcgtga cagtgctaca      120

tccttttcac tggactttgg ttatcttcgc aataagaacg gctgccacgt ggaattgctc      180

ttcctccgct acatctcgga ctgggaccta gaccctggcc gctgctaccg cgtcacctgg      240

ttcacctcct ggagcccctg ctacgactgt gcccgacatg tggccgactt tctgcgaggg      300

aaccccaacc tcagtctgag gatcttcacc gcgcgcctct acttctgtga ggaccgcaag      360

gctgagcccg aggggctgcg gcggctgcac cgcgccgggg tgcaaatagc catcatgacc      420

ttcaaagatt atttttactg ctggaatact tttgtagaaa accatgaaag aactttcaaa      480

gcctgggaag ggctgcatga aaattcagtt cgtctctcca gacagcttcg gcgcatcctt      540

ttgcccctgt atgaggttga tgacttacga gacgcatttc gtactttggg actt            594


<210>  24
<211>  198
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  wtAID protein seq

<400>  24

Met Asp Ser Leu Leu Met Asn Arg Arg Lys Phe Leu Tyr Gln Phe Lys 
1               5                   10                  15      


Asn Val Arg Trp Ala Lys Gly Arg Arg Glu Thr Tyr Leu Cys Tyr Val 
            20                  25                  30          


Val Lys Arg Arg Asp Ser Ala Thr Ser Phe Ser Leu Asp Phe Gly Tyr 
        35                  40                  45              


Leu Arg Asn Lys Asn Gly Cys His Val Glu Leu Leu Phe Leu Arg Tyr 
    50                  55                  60                  


Ile Ser Asp Trp Asp Leu Asp Pro Gly Arg Cys Tyr Arg Val Thr Trp 
65                  70                  75                  80  


Phe Thr Ser Trp Ser Pro Cys Tyr Asp Cys Ala Arg His Val Ala Asp 
                85                  90                  95      


Phe Leu Arg Gly Asn Pro Asn Leu Ser Leu Arg Ile Phe Thr Ala Arg 
            100                 105                 110         


Leu Tyr Phe Cys Glu Asp Arg Lys Ala Glu Pro Glu Gly Leu Arg Arg 
        115                 120                 125             


Leu His Arg Ala Gly Val Gln Ile Ala Ile Met Thr Phe Lys Asp Tyr 
    130                 135                 140                 


Phe Tyr Cys Trp Asn Thr Phe Val Glu Asn His Glu Arg Thr Phe Lys 
145                 150                 155                 160 


Ala Trp Glu Gly Leu His Glu Asn Ser Val Arg Leu Ser Arg Gln Leu 
                165                 170                 175     


Arg Arg Ile Leu Leu Pro Leu Tyr Glu Val Asp Asp Leu Arg Asp Ala 
            180                 185                 190         


Phe Arg Thr Leu Gly Leu 
        195             


<210>  25
<211>  594
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AID_S38A cDNA seq

<400>  25
atggacagcc tcttgatgaa ccggaggaag tttctttacc aattcaaaaa tgtccgctgg       60

gctaagggtc ggcgtgagac ctacctgtgc tacgtagtga agaggcgtga cgccgctaca      120

tccttttcac tggactttgg ttatcttcgc aataagaacg gctgccacgt ggaattgctc      180

ttcctccgct acatctcgga ctgggaccta gaccctggcc gctgctaccg cgtcacctgg      240

ttcacctcct ggagcccctg ctacgactgt gcccgacatg tggccgactt tctgcgaggg      300

aaccccaacc tcagtctgag gatcttcacc gcgcgcctct acttctgtga ggaccgcaag      360

gctgagcccg aggggctgcg gcggctgcac cgcgccgggg tgcaaatagc catcatgacc      420

ttcaaagatt atttttactg ctggaatact tttgtagaaa accatgaaag aactttcaaa      480

gcctgggaag ggctgcatga aaattcagtt cgtctctcca gacagcttcg gcgcatcctt      540

ttgcccctgt atgaggttga tgacttacga gacgcatttc gtactttggg actt            594


<210>  26
<211>  198
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AID_S38A protein seq

<400>  26

Met Asp Ser Leu Leu Met Asn Arg Arg Lys Phe Leu Tyr Gln Phe Lys 
1               5                   10                  15      


Asn Val Arg Trp Ala Lys Gly Arg Arg Glu Thr Tyr Leu Cys Tyr Val 
            20                  25                  30          


Val Lys Arg Arg Asp Ala Ala Thr Ser Phe Ser Leu Asp Phe Gly Tyr 
        35                  40                  45              


Leu Arg Asn Lys Asn Gly Cys His Val Glu Leu Leu Phe Leu Arg Tyr 
    50                  55                  60                  


Ile Ser Asp Trp Asp Leu Asp Pro Gly Arg Cys Tyr Arg Val Thr Trp 
65                  70                  75                  80  


Phe Thr Ser Trp Ser Pro Cys Tyr Asp Cys Ala Arg His Val Ala Asp 
                85                  90                  95      


Phe Leu Arg Gly Asn Pro Asn Leu Ser Leu Arg Ile Phe Thr Ala Arg 
            100                 105                 110         


Leu Tyr Phe Cys Glu Asp Arg Lys Ala Glu Pro Glu Gly Leu Arg Arg 
        115                 120                 125             


Leu His Arg Ala Gly Val Gln Ile Ala Ile Met Thr Phe Lys Asp Tyr 
    130                 135                 140                 


Phe Tyr Cys Trp Asn Thr Phe Val Glu Asn His Glu Arg Thr Phe Lys 
145                 150                 155                 160 


Ala Trp Glu Gly Leu His Glu Asn Ser Val Arg Leu Ser Arg Gln Leu 
                165                 170                 175     


Arg Arg Ile Leu Leu Pro Leu Tyr Glu Val Asp Asp Leu Arg Asp Ala 
            180                 185                 190         


Phe Arg Thr Leu Gly Leu 
        195             


<210>  27
<211>  624
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanised nucleotide sequence PmCDA1 (Petromyzon marinus)

<400>  27
atgaccgacg ctgaatacgt caggatacac gaaaagctcg atatttacac ctttaagaaa       60

cagttcttca ataataagaa gagtgtttca catcgatgct atgtgctttt cgagctcaaa      120

cggcgaggag aaaggagagc atgtttttgg ggctacgctg taaacaaacc ccaatctggc      180

acagagcggg gcattcacgc cgaaattttt tccatcagga aagtcgagga atacttgcgc      240

gataaccccg gtcaatttac aatcaactgg tattcttcat ggtccccctg cgctgactgc      300

gccgaaaaga tcttggaatg gtataaccag gaacttagag gtaacggtca cactctcaaa      360

atatgggcct gcaaacttta ctacgagaag aatgctcgaa accaaatagg cctgtggaat      420

cttcgcgata acggggtggg acttaatgtc atggtaagcg aacactacca atgctgccgc      480

aagattttta tacagtctag tcataaccag cttaacgaga accgctggct tgaaaagacg      540

ctcaaacggg cggaaaaaag gaggagtgag ctcagtataa tgattcaagt gaaaatactg      600

cacacgacta agtcaccagc agta                                             624


<210>  28
<211>  208
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence PmCDA1

<400>  28

Met Thr Asp Ala Glu Tyr Val Arg Ile His Glu Lys Leu Asp Ile Tyr 
1               5                   10                  15      


Thr Phe Lys Lys Gln Phe Phe Asn Asn Lys Lys Ser Val Ser His Arg 
            20                  25                  30          


Cys Tyr Val Leu Phe Glu Leu Lys Arg Arg Gly Glu Arg Arg Ala Cys 
        35                  40                  45              


Phe Trp Gly Tyr Ala Val Asn Lys Pro Gln Ser Gly Thr Glu Arg Gly 
    50                  55                  60                  


Ile His Ala Glu Ile Phe Ser Ile Arg Lys Val Glu Glu Tyr Leu Arg 
65                  70                  75                  80  


Asp Asn Pro Gly Gln Phe Thr Ile Asn Trp Tyr Ser Ser Trp Ser Pro 
                85                  90                  95      


Cys Ala Asp Cys Ala Glu Lys Ile Leu Glu Trp Tyr Asn Gln Glu Leu 
            100                 105                 110         


Arg Gly Asn Gly His Thr Leu Lys Ile Trp Ala Cys Lys Leu Tyr Tyr 
        115                 120                 125             


Glu Lys Asn Ala Arg Asn Gln Ile Gly Leu Trp Asn Leu Arg Asp Asn 
    130                 135                 140                 


Gly Val Gly Leu Asn Val Met Val Ser Glu His Tyr Gln Cys Cys Arg 
145                 150                 155                 160 


Lys Ile Phe Ile Gln Ser Ser His Asn Gln Leu Asn Glu Asn Arg Trp 
                165                 170                 175     


Leu Glu Lys Thr Leu Lys Arg Ala Glu Lys Arg Arg Ser Glu Leu Ser 
            180                 185                 190         


Ile Met Ile Gln Val Lys Ile Leu His Thr Thr Lys Ser Pro Ala Val 
        195                 200                 205             


<210>  29
<211>  350
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PmCDA1-linker-MCP seq

<400>  29

Met Thr Asp Ala Glu Tyr Val Arg Ile His Glu Lys Leu Asp Ile Tyr 
1               5                   10                  15      


Thr Phe Lys Lys Gln Phe Phe Asn Asn Lys Lys Ser Val Ser His Arg 
            20                  25                  30          


Cys Tyr Val Leu Phe Glu Leu Lys Arg Arg Gly Glu Arg Arg Ala Cys 
        35                  40                  45              


Phe Trp Gly Tyr Ala Val Asn Lys Pro Gln Ser Gly Thr Glu Arg Gly 
    50                  55                  60                  


Ile His Ala Glu Ile Phe Ser Ile Arg Lys Val Glu Glu Tyr Leu Arg 
65                  70                  75                  80  


Asp Asn Pro Gly Gln Phe Thr Ile Asn Trp Tyr Ser Ser Trp Ser Pro 
                85                  90                  95      


Cys Ala Asp Cys Ala Glu Lys Ile Leu Glu Trp Tyr Asn Gln Glu Leu 
            100                 105                 110         


Arg Gly Asn Gly His Thr Leu Lys Ile Trp Ala Cys Lys Leu Tyr Tyr 
        115                 120                 125             


Glu Lys Asn Ala Arg Asn Gln Ile Gly Leu Trp Asn Leu Arg Asp Asn 
    130                 135                 140                 


Gly Val Gly Leu Asn Val Met Val Ser Glu His Tyr Gln Cys Cys Arg 
145                 150                 155                 160 


Lys Ile Phe Ile Gln Ser Ser His Asn Gln Leu Asn Glu Asn Arg Trp 
                165                 170                 175     


Leu Glu Lys Thr Leu Lys Arg Ala Glu Lys Arg Arg Ser Glu Leu Ser 
            180                 185                 190         


Ile Met Ile Gln Val Lys Ile Leu His Thr Thr Lys Ser Pro Ala Val 
        195                 200                 205             


Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Ser Pro Pro Cys 
    210                 215                 220                 


Pro Ala Pro Glu Leu Leu Gly Gly Pro Met Ala Ser Asn Phe Thr Gln 
225                 230                 235                 240 


Phe Val Leu Val Asp Asn Gly Gly Thr Gly Asp Val Thr Val Ala Pro 
                245                 250                 255     


Ser Asn Phe Ala Asn Gly Ile Ala Glu Trp Ile Ser Ser Asn Ser Arg 
            260                 265                 270         


Ser Gln Ala Tyr Lys Val Thr Cys Ser Val Arg Gln Ser Ser Ala Gln 
        275                 280                 285             


Asn Arg Lys Tyr Thr Ile Lys Val Glu Val Pro Lys Gly Ala Trp Arg 
    290                 295                 300                 


Ser Tyr Leu Asn Met Glu Leu Thr Ile Pro Ile Phe Ala Thr Asn Ser 
305                 310                 315                 320 


Asp Cys Glu Leu Ile Val Lys Ala Met Gln Gly Leu Leu Lys Asp Gly 
                325                 330                 335     


Asn Pro Ile Pro Ser Ala Ile Ala Ala Asn Ser Gly Ile Tyr 
            340                 345                 350 


<210>  30
<211>  135
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Sequence of gRNA_MS2 construct


<220>
<221>  misc_feature
<222>  (1)..(20)
<223>  n is a, c, g, or u

<400>  30
nnnnnnnnnn nnnnnnnnnn guuuuagagc uaugcuguug aaaaacagca uagcaaguua       60

aaauaaggcu aguccguuau caacuugaaa aaguggcacc gagucggugc gcgcacauga      120

ggaucaccca ugugc                                                       135


<210>  31
<211>  149
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Sequence of gRNA_2xMS2 construct


<220>
<221>  misc_feature
<222>  (1)..(19)
<223>  n is a, c, g, or u

<400>  31
nnnnnnnnnn nnnnnnnnng uuuuagagcu agaaauagca aguuaaaaua aggcuagucc       60

guuaucaacu ugaaaaagug gcaccgaguc ggugcgggag cacaugagga ucacccaugu      120

gccacgagcg acaugaggau cacccaugu                                        149


<210>  32
<211>  42
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic crRNA Sequence


<220>
<221>  m
<222>  (1)..(2)
<223>  2'Oxymethyl

<220>
<221>  Phosphorothioate-bonds
<222>  (1)..(3)
<223>  Phosphorothioate bonds between bases 1&2, 2&3

<400>  32
cacctaccta agaaccatcc guuuuagagc uaugcuguuu ug                          42


<210>  33
<211>  99
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic tracrRNA-MS2 Aptamer Sequence


<220>
<221>  m
<222>  (97)..(98)
<223>  2'Oxymethyl modification

<220>
<221>  Phosphorothioate-bonds
<222>  (97)..(99)
<223>  Phosphorothioate bonds between bases 97&98, 98&99

<400>  33
aacagcauag caaguuaaaa uaaggcuagu ccguuaucaa cuugaaaaag uggcaccgag       60

ucggugcgcg cacaugagga ucacccaugu gcuuuuuuu                              99


<210>  34
<211>  128
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  B2M sgRNA seq


<220>
<221>  m
<222>  (1)..(2)
<223>  2'Oxymethyl modification

<220>
<221>  Phosphorothioate-bonds
<222>  (1)..(3)
<223>  Phosphorothioate bonds between bases 1&2, 2&3

<220>
<221>  m
<222>  (126)..(127)
<223>  2'Oxymethyl modification

<220>
<221>  Phosphorothioate-bonds
<222>  (126)..(128)
<223>  Phosphorothioate bonds between bases 126&127, 127&128

<400>  34
uucguaucug uaaaaccaag guuuuagagc uagaaauagc aaguuaaaau aaggcuaguc       60

cguuaucaac uugaaaaagu ggcaccgagu cggugcgcgc acaugaggau cacccaugug      120

cuuuuuuu                                                               128


<210>  35
<211>  128
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  CD52 sgRNA seq


<220>
<221>  m
<222>  (1)..(2)
<223>  2'Oxymethyl modification

<220>
<221>  Phosphorothioate-bonds
<222>  (1)..(3)
<223>  Phosphorothioate bonds between bases 1&2, 2&3

<220>
<221>  m
<222>  (126)..(127)
<223>  2'Oxymethyl modification

<220>
<221>  Phosphorothioate-bonds
<222>  (126)..(128)
<223>  Phosphorothioate bonds between bases 126&127, 127&128

<400>  35
acucacgcug gauagccucc guuuuagagc uagaaauagc aaguuaaaau aaggcuaguc       60

cguuaucaac uugaaaaagu ggcaccgagu cggugcgcgc acaugaggau cacccaugug      120

cuuuuuuu                                                               128


<210>  36
<211>  128
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  TRAC sgRNA seq


<220>
<221>  m
<222>  (1)..(2)
<223>  2'Oxymethyl modification

<220>
<221>  Phosphorothioate-bonds
<222>  (1)..(3)
<223>  Phosphorothioate bonds between bases 1&2, 2&3

<220>
<221>  m
<222>  (126)..(127)
<223>  2'Oxymethyl modification

<220>
<221>  Phosphorothioate-bonds
<222>  (126)..(128)
<223>  Phosphorothioate bonds between bases 126&127, 127&128

<400>  36
cucuuaccug uaccauaacc guuuuagagc uagaaauagc aaguuaaaau aaggcuaguc       60

cguuaucaac uugaaaaagu ggcaccgagu cggugcgcgc acaugaggau cacccaugug      120

cuuuuuuu                                                               128


<210>  37
<211>  128
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  PDCD-1 sgRNA seq


<220>
<221>  m
<222>  (1)..(2)
<223>  2'Oxymethyl modification

<220>
<221>  Phosphorothioate-bonds
<222>  (1)..(3)
<223>  Phosphorothioate bonds between bases 1&2, 2&3

<220>
<221>  m
<222>  (126)..(127)
<223>  2'Oxymethyl modification

<220>
<221>  Phosphorothioate-bonds
<222>  (126)..(128)
<223>  Phosphorothioate bonds between bases 126&127, 127&128

<400>  37
caccuaccua agaaccaucc guuuuagagc uagaaauagc aaguuaaaau aaggcuaguc       60

cguuaucaac uugaaaaagu ggcaccgagu cggugcgcgc acaugaggau cacccaugug      120

cuuuuuuu                                                               128


<210>  38
<211>  128
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Scramble sgRNA seq


<220>
<221>  m
<222>  (1)..(2)
<223>  2'Oxymethyl modification

<220>
<221>  Phosphorothioate-bonds
<222>  (1)..(3)
<223>  Phosphorothioate bonds between bases 1&2, 2&3

<220>
<221>  m
<222>  (126)..(127)
<223>  2'Oxymethyl modification

<220>
<221>  Phosphorothioate-bonds
<222>  (126)..(128)
<223>  Phosphorothioate bonds between bases 126&127, 127&128

<400>  38
gcacuaccag agcuaacuca guuuuagagc uagaaauagc aaguuaaaau aaggcuaguc       60

cguuaucaac uugaaaaagu ggcaccgagu cggugcgcgc acaugaggau cacccaugug      120

cuuuuuuu                                                               128


<210>  39
<211>  319
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NLS-Anolis(P16A-E17A)-Apobec1-Linker-MCP seq

<400>  39

Met Ala Pro Lys Lys Lys Arg Lys Val Met Glu Pro Glu Ala Phe Gln 
1               5                   10                  15      


Arg Asn Phe Asp Pro Arg Glu Phe Ala Ala Cys Thr Leu Leu Leu Tyr 
            20                  25                  30          


Glu Ile His Trp Asp Asn Asn Thr Ser Arg Asn Trp Cys Thr Asn Lys 
        35                  40                  45              


Pro Gly Leu His Ala Glu Glu Asn Phe Leu Gln Ile Phe Asn Glu Lys 
    50                  55                  60                  


Ile Asp Ile Lys Gln Asp Thr Pro Cys Ser Ile Thr Trp Phe Leu Ser 
65                  70                  75                  80  


Trp Ser Pro Cys Tyr Pro Cys Ser Gln Ala Ile Ile Lys Phe Leu Glu 
                85                  90                  95      


Ala His Pro Asn Val Ser Leu Glu Ile Lys Ala Ala Arg Leu Tyr Met 
            100                 105                 110         


His Gln Ile Asp Cys Asn Lys Glu Gly Leu Arg Asn Leu Gly Arg Asn 
        115                 120                 125             


Arg Val Ser Ile Met Asn Leu Pro Asp Tyr Arg His Cys Trp Thr Thr 
    130                 135                 140                 


Phe Val Val Pro Arg Gly Ala Asn Glu Asp Tyr Trp Pro Gln Asp Phe 
145                 150                 155                 160 


Leu Pro Ala Ile Thr Asn Tyr Ser Arg Glu Leu Asp Ser Ile Leu Gln 
                165                 170                 175     


Asp Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Ser Pro Pro 
            180                 185                 190         


Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Met Ala Ser Asn Phe Thr 
        195                 200                 205             


Gln Phe Val Leu Val Asp Asn Gly Gly Thr Gly Asp Val Thr Val Ala 
    210                 215                 220                 


Pro Ser Asn Phe Ala Asn Gly Ile Ala Glu Trp Ile Ser Ser Asn Ser 
225                 230                 235                 240 


Arg Ser Gln Ala Tyr Lys Val Thr Cys Ser Val Arg Gln Ser Ser Ala 
                245                 250                 255     


Gln Asn Arg Lys Tyr Thr Ile Lys Val Glu Val Pro Lys Gly Ala Trp 
            260                 265                 270         


Arg Ser Tyr Leu Asn Met Glu Leu Thr Ile Pro Ile Phe Ala Thr Asn 
        275                 280                 285             


Ser Asp Cys Glu Leu Ile Val Lys Ala Met Gln Gly Leu Leu Lys Asp 
    290                 295                 300                 


Gly Asn Pro Ile Pro Ser Ala Ile Ala Ala Asn Ser Gly Ile Tyr 
305                 310                 315                 


<210>  40
<211>  379
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NLS-Rattus-Apobec1-Linker-MCP seq

<400>  40

Met Ala Pro Lys Lys Lys Arg Lys Val Ser Ser Glu Thr Gly Pro Val 
1               5                   10                  15      


Ala Val Asp Pro Thr Leu Arg Arg Arg Ile Glu Pro His Glu Phe Glu 
            20                  25                  30          


Val Phe Phe Asp Pro Arg Glu Leu Arg Lys Glu Thr Cys Leu Leu Tyr 
        35                  40                  45              


Glu Ile Asn Trp Gly Gly Arg His Ser Ile Trp Arg His Thr Ser Gln 
    50                  55                  60                  


Asn Thr Asn Lys His Val Glu Val Asn Phe Ile Glu Lys Phe Thr Thr 
65                  70                  75                  80  


Glu Arg Tyr Phe Cys Pro Asn Thr Arg Cys Ser Ile Thr Trp Phe Leu 
                85                  90                  95      


Ser Trp Ser Pro Cys Gly Glu Cys Ser Arg Ala Ile Thr Glu Phe Leu 
            100                 105                 110         


Ser Arg Tyr Pro His Val Thr Leu Phe Ile Tyr Ile Ala Arg Leu Tyr 
        115                 120                 125             


His His Ala Asp Pro Arg Asn Arg Gln Gly Leu Arg Asp Leu Ile Ser 
    130                 135                 140                 


Ser Gly Val Thr Ile Gln Ile Met Thr Glu Gln Glu Ser Gly Tyr Cys 
145                 150                 155                 160 


Trp Arg Asn Phe Val Asn Tyr Ser Pro Ser Asn Glu Ala His Trp Pro 
                165                 170                 175     


Arg Tyr Pro His Leu Trp Val Arg Leu Tyr Val Leu Glu Leu Tyr Cys 
            180                 185                 190         


Ile Ile Leu Gly Leu Pro Pro Cys Leu Asn Ile Leu Arg Arg Lys Gln 
        195                 200                 205             


Pro Gln Leu Thr Phe Phe Thr Ile Ala Leu Gln Ser Cys His Tyr Gln 
    210                 215                 220                 


Arg Leu Pro Pro His Ile Leu Trp Ala Thr Gly Leu Lys Glu Leu Lys 
225                 230                 235                 240 


Thr Pro Leu Gly Asp Thr Thr His Thr Ser Pro Pro Cys Pro Ala Pro 
                245                 250                 255     


Glu Leu Leu Gly Gly Pro Met Ala Ser Asn Phe Thr Gln Phe Val Leu 
            260                 265                 270         


Val Asp Asn Gly Gly Thr Gly Asp Val Thr Val Ala Pro Ser Asn Phe 
        275                 280                 285             


Ala Asn Gly Ile Ala Glu Trp Ile Ser Ser Asn Ser Arg Ser Gln Ala 
    290                 295                 300                 


Tyr Lys Val Thr Cys Ser Val Arg Gln Ser Ser Ala Gln Asn Arg Lys 
305                 310                 315                 320 


Tyr Thr Ile Lys Val Glu Val Pro Lys Gly Ala Trp Arg Ser Tyr Leu 
                325                 330                 335     


Asn Met Glu Leu Thr Ile Pro Ile Phe Ala Thr Asn Ser Asp Cys Glu 
            340                 345                 350         


Leu Ile Val Lys Ala Met Gln Gly Leu Leu Lys Asp Gly Asn Pro Ile 
        355                 360                 365             


Pro Ser Ala Ile Ala Ala Asn Ser Gly Ile Tyr 
    370                 375                 


<210>  41
<211>  349
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NLS-Homo-AID-L25-MCP seq

<400>  41

Met Ala Pro Lys Lys Lys Arg Lys Val Met Asp Ser Leu Leu Met Asn 
1               5                   10                  15      


Arg Arg Lys Phe Leu Tyr Gln Phe Lys Asn Val Arg Trp Ala Lys Gly 
            20                  25                  30          


Arg Arg Glu Thr Tyr Leu Cys Tyr Val Val Lys Arg Arg Asp Ser Ala 
        35                  40                  45              


Thr Ser Phe Ser Leu Asp Phe Gly Tyr Leu Arg Asn Lys Asn Gly Cys 
    50                  55                  60                  


His Val Glu Leu Leu Phe Leu Arg Tyr Ile Ser Asp Trp Asp Leu Asp 
65                  70                  75                  80  


Pro Gly Arg Cys Tyr Arg Val Thr Trp Phe Thr Ser Trp Ser Pro Cys 
                85                  90                  95      


Tyr Asp Cys Ala Arg His Val Ala Asp Phe Leu Arg Gly Asn Pro Asn 
            100                 105                 110         


Leu Ser Leu Arg Ile Phe Thr Ala Arg Leu Tyr Phe Cys Glu Asp Arg 
        115                 120                 125             


Lys Ala Glu Pro Glu Gly Leu Arg Arg Leu His Arg Ala Gly Val Gln 
    130                 135                 140                 


Ile Ala Ile Met Thr Phe Lys Asp Tyr Phe Tyr Cys Trp Asn Thr Phe 
145                 150                 155                 160 


Val Glu Asn His Glu Arg Thr Phe Lys Ala Trp Glu Gly Leu His Glu 
                165                 170                 175     


Asn Ser Val Arg Leu Ser Arg Gln Leu Arg Arg Ile Leu Leu Pro Leu 
            180                 185                 190         


Tyr Glu Val Asp Asp Leu Arg Asp Ala Phe Arg Thr Leu Gly Leu Glu 
        195                 200                 205             


Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Ser Pro Pro Cys Pro 
    210                 215                 220                 


Ala Pro Glu Leu Leu Gly Gly Pro Met Ala Ser Asn Phe Thr Gln Phe 
225                 230                 235                 240 


Val Leu Val Asp Asn Gly Gly Thr Gly Asp Val Thr Val Ala Pro Ser 
                245                 250                 255     


Asn Phe Ala Asn Gly Ile Ala Glu Trp Ile Ser Ser Asn Ser Arg Ser 
            260                 265                 270         


Gln Ala Tyr Lys Val Thr Cys Ser Val Arg Gln Ser Ser Ala Gln Asn 
        275                 280                 285             


Arg Lys Tyr Thr Ile Lys Val Glu Val Pro Lys Gly Ala Trp Arg Ser 
    290                 295                 300                 


Tyr Leu Asn Met Glu Leu Thr Ile Pro Ile Phe Ala Thr Asn Ser Asp 
305                 310                 315                 320 


Cys Glu Leu Ile Val Lys Ala Met Gln Gly Leu Leu Lys Asp Gly Asn 
                325                 330                 335     


Pro Ile Pro Ser Ala Ile Ala Ala Asn Ser Gly Ile Tyr 
            340                 345                 


<210>  42
<211>  1582
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NLS-nCas9(D10A)-UGI-UGI-NLS seq

<400>  42

Met Pro Lys Lys Lys Arg Lys Val Asp Lys Lys Tyr Ser Ile Gly Leu 
1               5                   10                  15      


Ala Ile Gly Thr Asn Ser Val Gly Trp Ala Val Ile Thr Asp Glu Tyr 
            20                  25                  30          


Lys Val Pro Ser Lys Lys Phe Lys Val Leu Gly Asn Thr Asp Arg His 
        35                  40                  45              


Ser Ile Lys Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp Ser Gly Glu 
    50                  55                  60                  


Thr Ala Glu Ala Thr Arg Leu Lys Arg Thr Ala Arg Arg Arg Tyr Thr 
65                  70                  75                  80  


Arg Arg Lys Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe Ser Asn Glu 
                85                  90                  95      


Met Ala Lys Val Asp Asp Ser Phe Phe His Arg Leu Glu Glu Ser Phe 
            100                 105                 110         


Leu Val Glu Glu Asp Lys Lys His Glu Arg His Pro Ile Phe Gly Asn 
        115                 120                 125             


Ile Val Asp Glu Val Ala Tyr His Glu Lys Tyr Pro Thr Ile Tyr His 
    130                 135                 140                 


Leu Arg Lys Lys Leu Val Asp Ser Thr Asp Lys Ala Asp Leu Arg Leu 
145                 150                 155                 160 


Ile Tyr Leu Ala Leu Ala His Met Ile Lys Phe Arg Gly His Phe Leu 
                165                 170                 175     


Ile Glu Gly Asp Leu Asn Pro Asp Asn Ser Asp Val Asp Lys Leu Phe 
            180                 185                 190         


Ile Gln Leu Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu Asn Pro Ile 
        195                 200                 205             


Asn Ala Ser Gly Val Asp Ala Lys Ala Ile Leu Ser Ala Arg Leu Ser 
    210                 215                 220                 


Lys Ser Arg Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro Gly Glu Lys 
225                 230                 235                 240 


Lys Asn Gly Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu Gly Leu Thr 
                245                 250                 255     


Pro Asn Phe Lys Ser Asn Phe Asp Leu Ala Glu Asp Ala Lys Leu Gln 
            260                 265                 270         


Leu Ser Lys Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu Leu Ala Gln 
        275                 280                 285             


Ile Gly Asp Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys Asn Leu Ser 
    290                 295                 300                 


Asp Ala Ile Leu Leu Ser Asp Ile Leu Arg Val Asn Thr Glu Ile Thr 
305                 310                 315                 320 


Lys Ala Pro Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp Glu His His 
                325                 330                 335     


Gln Asp Leu Thr Leu Leu Lys Ala Leu Val Arg Gln Gln Leu Pro Glu 
            340                 345                 350         


Lys Tyr Lys Glu Ile Phe Phe Asp Gln Ser Lys Asn Gly Tyr Ala Gly 
        355                 360                 365             


Tyr Ile Asp Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys Phe Ile Lys 
    370                 375                 380                 


Pro Ile Leu Glu Lys Met Asp Gly Thr Glu Glu Leu Leu Val Lys Leu 
385                 390                 395                 400 


Asn Arg Glu Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp Asn Gly Ser 
                405                 410                 415     


Ile Pro His Gln Ile His Leu Gly Glu Leu His Ala Ile Leu Arg Arg 
            420                 425                 430         


Gln Glu Asp Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu Lys Ile Glu 
        435                 440                 445             


Lys Ile Leu Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro Leu Ala Arg 
    450                 455                 460                 


Gly Asn Ser Arg Phe Ala Trp Met Thr Arg Lys Ser Glu Glu Thr Ile 
465                 470                 475                 480 


Thr Pro Trp Asn Phe Glu Glu Val Val Asp Lys Gly Ala Ser Ala Gln 
                485                 490                 495     


Ser Phe Ile Glu Arg Met Thr Asn Phe Asp Lys Asn Leu Pro Asn Glu 
            500                 505                 510         


Lys Val Leu Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe Thr Val Tyr 
        515                 520                 525             


Asn Glu Leu Thr Lys Val Lys Tyr Val Thr Glu Gly Met Arg Lys Pro 
    530                 535                 540                 


Ala Phe Leu Ser Gly Glu Gln Lys Lys Ala Ile Val Asp Leu Leu Phe 
545                 550                 555                 560 


Lys Thr Asn Arg Lys Val Thr Val Lys Gln Leu Lys Glu Asp Tyr Phe 
                565                 570                 575     


Lys Lys Ile Glu Cys Phe Asp Ser Val Glu Ile Ser Gly Val Glu Asp 
            580                 585                 590         


Arg Phe Asn Ala Ser Leu Gly Thr Tyr His Asp Leu Leu Lys Ile Ile 
        595                 600                 605             


Lys Asp Lys Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile Leu Glu 
    610                 615                 620                 


Asp Ile Val Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu Met Ile Glu 
625                 630                 635                 640 


Glu Arg Leu Lys Thr Tyr Ala His Leu Phe Asp Asp Lys Val Met Lys 
                645                 650                 655     


Gln Leu Lys Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser Arg Lys 
            660                 665                 670         


Leu Ile Asn Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile Leu Asp 
        675                 680                 685             


Phe Leu Lys Ser Asp Gly Phe Ala Asn Arg Asn Phe Met Gln Leu Ile 
    690                 695                 700                 


His Asp Asp Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala Gln Val 
705                 710                 715                 720 


Ser Gly Gln Gly Asp Ser Leu His Glu His Ile Ala Asn Leu Ala Gly 
                725                 730                 735     


Ser Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val Asp 
            740                 745                 750         


Glu Leu Val Lys Val Met Gly Arg His Lys Pro Glu Asn Ile Val Ile 
        755                 760                 765             


Glu Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser 
    770                 775                 780                 


Arg Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser 
785                 790                 795                 800 


Gln Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn Glu 
                805                 810                 815     


Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val Asp 
            820                 825                 830         


Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp His Ile 
        835                 840                 845             


Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn Lys Val Leu 
    850                 855                 860                 


Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn Val Pro Ser Glu 
865                 870                 875                 880 


Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg Gln Leu Leu Asn Ala 
                885                 890                 895     


Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn Leu Thr Lys Ala Glu Arg 
            900                 905                 910         


Gly Gly Leu Ser Glu Leu Asp Lys Ala Gly Phe Ile Lys Arg Gln Leu 
        915                 920                 925             


Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Gln Ile Leu Asp Ser 
    930                 935                 940                 


Arg Met Asn Thr Lys Tyr Asp Glu Asn Asp Lys Leu Ile Arg Glu Val 
945                 950                 955                 960 


Lys Val Ile Thr Leu Lys Ser Lys Leu Val Ser Asp Phe Arg Lys Asp 
                965                 970                 975     


Phe Gln Phe Tyr Lys Val Arg Glu Ile Asn Asn Tyr His His Ala His 
            980                 985                 990         


Asp Ala Tyr Leu Asn Ala Val Val  Gly Thr Ala Leu Ile  Lys Lys Tyr 
        995                 1000                 1005             


Pro Lys  Leu Glu Ser Glu Phe  Val Tyr Gly Asp Tyr  Lys Val Tyr 
    1010                 1015                 1020             


Asp Val  Arg Lys Met Ile Ala  Lys Ser Glu Gln Glu  Ile Gly Lys 
    1025                 1030                 1035             


Ala Thr  Ala Lys Tyr Phe Phe  Tyr Ser Asn Ile Met  Asn Phe Phe 
    1040                 1045                 1050             


Lys Thr  Glu Ile Thr Leu Ala  Asn Gly Glu Ile Arg  Lys Arg Pro 
    1055                 1060                 1065             


Leu Ile  Glu Thr Asn Gly Glu  Thr Gly Glu Ile Val  Trp Asp Lys 
    1070                 1075                 1080             


Gly Arg  Asp Phe Ala Thr Val  Arg Lys Val Leu Ser  Met Pro Gln 
    1085                 1090                 1095             


Val Asn  Ile Val Lys Lys Thr  Glu Val Gln Thr Gly  Gly Phe Ser 
    1100                 1105                 1110             


Lys Glu  Ser Ile Leu Pro Lys  Arg Asn Ser Asp Lys  Leu Ile Ala 
    1115                 1120                 1125             


Arg Lys  Lys Asp Trp Asp Pro  Lys Lys Tyr Gly Gly  Phe Asp Ser 
    1130                 1135                 1140             


Pro Thr  Val Ala Tyr Ser Val  Leu Val Val Ala Lys  Val Glu Lys 
    1145                 1150                 1155             


Gly Lys  Ser Lys Lys Leu Lys  Ser Val Lys Glu Leu  Leu Gly Ile 
    1160                 1165                 1170             


Thr Ile  Met Glu Arg Ser Ser  Phe Glu Lys Asn Pro  Ile Asp Phe 
    1175                 1180                 1185             


Leu Glu  Ala Lys Gly Tyr Lys  Glu Val Lys Lys Asp  Leu Ile Ile 
    1190                 1195                 1200             


Lys Leu  Pro Lys Tyr Ser Leu  Phe Glu Leu Glu Asn  Gly Arg Lys 
    1205                 1210                 1215             


Arg Met  Leu Ala Ser Ala Gly  Glu Leu Gln Lys Gly  Asn Glu Leu 
    1220                 1225                 1230             


Ala Leu  Pro Ser Lys Tyr Val  Asn Phe Leu Tyr Leu  Ala Ser His 
    1235                 1240                 1245             


Tyr Glu  Lys Leu Lys Gly Ser  Pro Glu Asp Asn Glu  Gln Lys Gln 
    1250                 1255                 1260             


Leu Phe  Val Glu Gln His Lys  His Tyr Leu Asp Glu  Ile Ile Glu 
    1265                 1270                 1275             


Gln Ile  Ser Glu Phe Ser Lys  Arg Val Ile Leu Ala  Asp Ala Asn 
    1280                 1285                 1290             


Leu Asp  Lys Val Leu Ser Ala  Tyr Asn Lys His Arg  Asp Lys Pro 
    1295                 1300                 1305             


Ile Arg  Glu Gln Ala Glu Asn  Ile Ile His Leu Phe  Thr Leu Thr 
    1310                 1315                 1320             


Asn Leu  Gly Ala Pro Ala Ala  Phe Lys Tyr Phe Asp  Thr Thr Ile 
    1325                 1330                 1335             


Asp Arg  Lys Arg Tyr Thr Ser  Thr Lys Glu Val Leu  Asp Ala Thr 
    1340                 1345                 1350             


Leu Ile  His Gln Ser Ile Thr  Gly Leu Tyr Glu Thr  Arg Ile Asp 
    1355                 1360                 1365             


Leu Ser  Gln Leu Gly Gly Asp  Ser Gly Gly Ser Gly  Gly Ser Gly 
    1370                 1375                 1380             


Gly Ser  Thr Asn Leu Ser Asp  Ile Ile Glu Lys Glu  Thr Gly Lys 
    1385                 1390                 1395             


Gln Leu  Val Ile Gln Glu Ser  Ile Leu Met Leu Pro  Glu Glu Val 
    1400                 1405                 1410             


Glu Glu  Val Ile Gly Asn Lys  Pro Glu Ser Asp Ile  Leu Val His 
    1415                 1420                 1425             


Thr Ala  Tyr Asp Glu Ser Thr  Asp Glu Asn Val Met  Leu Leu Thr 
    1430                 1435                 1440             


Ser Asp  Ala Pro Glu Tyr Lys  Pro Trp Ala Leu Val  Ile Gln Asp 
    1445                 1450                 1455             


Ser Asn  Gly Glu Asn Lys Ile  Lys Met Leu Ser Gly  Gly Ser Gly 
    1460                 1465                 1470             


Gly Ser  Gly Gly Ser Thr Asn  Leu Ser Asp Ile Ile  Glu Lys Glu 
    1475                 1480                 1485             


Thr Gly  Lys Gln Leu Val Ile  Gln Glu Ser Ile Leu  Met Leu Pro 
    1490                 1495                 1500             


Glu Glu  Val Glu Glu Val Ile  Gly Asn Lys Pro Glu  Ser Asp Ile 
    1505                 1510                 1515             


Leu Val  His Thr Ala Tyr Asp  Glu Ser Thr Asp Glu  Asn Val Met 
    1520                 1525                 1530             


Leu Leu  Thr Ser Asp Ala Pro  Glu Tyr Lys Pro Trp  Ala Leu Val 
    1535                 1540                 1545             


Ile Gln  Asp Ser Asn Gly Glu  Asn Lys Ile Lys Met  Leu Ser Gly 
    1550                 1555                 1560             


Gly Ser  Lys Arg Thr Ala Asp  Gly Ser Glu Phe Glu  Pro Lys Lys 
    1565                 1570                 1575             


Lys Arg  Lys Val 
    1580         


<210>  43
<211>  4104
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanised nucleotide sequence WT Streptococcus pyogenes Cas9

<400>  43
atggacaaga agtacagcat cggcctggac atcggcacca actctgtggg ctgggccgtg       60

atcaccgacg agtacaaggt gcccagcaag aaattcaagg tgctgggcaa caccgaccgg      120

cacagcatca agaagaacct gatcggagcc ctgctgttcg acagcggcga aacagccgag      180

gccacccggc tgaagagaac cgccagaaga agatacacca gacggaagaa ccggatctgc      240

tatctgcaag agatcttcag caacgagatg gccaaggtgg acgacagctt cttccacaga      300

ctggaagagt ccttcctggt ggaagaggat aagaagcacg agcggcaccc catcttcggc      360

aacatcgtgg acgaggtggc ctaccacgag aagtacccca ccatctacca cctgagaaag      420

aaactggtgg acagcaccga caaggccgac ctgcggctga tctatctggc cctggcccac      480

atgatcaagt tccggggcca cttcctgatc gagggcgacc tgaaccccga caacagcgac      540

gtggacaagc tgttcatcca gctggtgcag acctacaacc agctgttcga ggaaaacccc      600

atcaacgcca gcggcgtgga cgccaaggcc atcctgtctg ccagactgag caagagcaga      660

cggctggaaa atctgatcgc ccagctgccc ggcgagaaga agaatggcct gttcggaaac      720

ctgattgccc tgagcctggg cctgaccccc aacttcaaga gcaacttcga cctggccgag      780

gatgccaaac tgcagctgag caaggacacc tacgacgacg acctggacaa cctgctggcc      840

cagatcggcg accagtacgc cgacctgttt ctggccgcca agaacctgtc cgacgccatc      900

ctgctgagcg acatcctgag agtgaacacc gagatcacca aggcccccct gagcgcctct      960

atgatcaaga gatacgacga gcaccaccag gacctgaccc tgctgaaagc tctcgtgcgg     1020

cagcagctgc ctgagaagta caaagagatt ttcttcgacc agagcaagaa cggctacgcc     1080

ggctacattg acggcggagc cagccaggaa gagttctaca agttcatcaa gcccatcctg     1140

gaaaagatgg acggcaccga ggaactgctc gtgaagctga acagagagga cctgctgcgg     1200

aagcagcgga ccttcgacaa cggcagcatc ccccaccaga tccacctggg agagctgcac     1260

gccattctgc ggcggcagga agatttttac ccattcctga aggacaaccg ggaaaagatc     1320

gagaagatcc tgaccttccg catcccctac tacgtgggcc ctctggccag gggaaacagc     1380

agattcgcct ggatgaccag aaagagcgag gaaaccatca ccccctggaa cttcgaggaa     1440

gtggtggaca agggcgcttc cgcccagagc ttcatcgagc ggatgaccaa cttcgataag     1500

aacctgccca acgagaaggt gctgcccaag cacagcctgc tgtacgagta cttcaccgtg     1560

tataacgagc tgaccaaagt gaaatacgtg accgagggaa tgagaaagcc cgccttcctg     1620

agcggcgagc agaaaaaggc catcgtggac ctgctgttca agaccaaccg gaaagtgacc     1680

gtgaagcagc tgaaagagga ctacttcaag aaaatcgagt gcttcgactc cgtggaaatc     1740

tccggcgtgg aagatcggtt caacgcctcc ctgggcacat accacgatct gctgaaaatt     1800

atcaaggaca aggacttcct ggacaatgag gaaaacgagg acattctgga agatatcgtg     1860

ctgaccctga cactgtttga ggacagagag atgatcgagg aacggctgaa aacctatgcc     1920

cacctgttcg acgacaaagt gatgaagcag ctgaagcggc ggagatacac cggctggggc     1980

aggctgagcc ggaagctgat caacggcatc cgggacaagc agtccggcaa gacaatcctg     2040

gatttcctga agtccgacgg cttcgccaac agaaacttca tgcagctgat ccacgacgac     2100

agcctgacct ttaaagagga catccagaaa gcccaggtgt ccggccaggg cgatagcctg     2160

cacgagcaca ttgccaatct ggccggcagc cccgccatta agaagggcat cctgcagaca     2220

gtgaaggtgg tggacgagct cgtgaaagtg atgggccggc acaagcccga gaacatcgtg     2280

atcgaaatgg ccagagagaa ccagaccacc cagaagggac agaagaacag ccgcgagaga     2340

atgaagcgga tcgaagaggg catcaaagag ctgggcagcc agatcctgaa agaacacccc     2400

gtggaaaaca cccagctgca gaacgagaag ctgtacctgt actacctgca gaatgggcgg     2460

gatatgtacg tggaccagga actggacatc aaccggctgt ccgactacga tgtggaccat     2520

atcgtgcctc agagctttct gaaggacgac tccatcgaca acaaggtgct gaccagaagc     2580

gacaagaacc ggggcaagag cgacaacgtg ccctccgaag aggtcgtgaa gaagatgaag     2640

aactactggc ggcagctgct gaacgccaag ctgattaccc agagaaagtt cgacaatctg     2700

accaaggccg agagaggcgg cctgagcgaa ctggataagg ccggcttcat caagagacag     2760

ctggtggaaa cccggcagat cacaaagcac gtggcacaga tcctggactc ccggatgaac     2820

actaagtacg acgagaatga caagctgatc cgggaagtga aagtgatcac cctgaagtcc     2880

aagctggtgt ccgatttccg gaaggatttc cagttttaca aagtgcgcga gatcaacaac     2940

taccaccacg cccacgacgc ctacctgaac gccgtcgtgg gaaccgccct gatcaaaaag     3000

taccctaagc tggaaagcga gttcgtgtac ggcgactaca aggtgtacga cgtgcggaag     3060

atgatcgcca agagcgagca ggaaatcggc aaggctaccg ccaagtactt cttctacagc     3120

aacatcatga actttttcaa gaccgagatt accctggcca acggcgagat ccggaagcgg     3180

cctctgatcg agacaaacgg cgaaaccggg gagatcgtgt gggataaggg ccgggatttt     3240

gccaccgtgc ggaaagtgct gagcatgccc caagtgaata tcgtgaaaaa gaccgaggtg     3300

cagacaggcg gcttcagcaa agagtctatc ctgcccaaga ggaacagcga taagctgatc     3360

gccagaaaga aggactggga ccctaagaag tacggcggct tcgacagccc caccgtggcc     3420

tattctgtgc tggtggtggc caaagtggaa aagggcaagt ccaagaaact gaagagtgtg     3480

aaagagctgc tggggatcac catcatggaa agaagcagct tcgagaagaa tcccatcgac     3540

tttctggaag ccaagggcta caaagaagtg aaaaaggacc tgatcatcaa gctgcctaag     3600

tactccctgt tcgagctgga aaacggccgg aagagaatgc tggcctctgc cggcgaactg     3660

cagaagggaa acgaactggc cctgccctcc aaatatgtga acttcctgta cctggccagc     3720

cactatgaga agctgaaggg ctcccccgag gataatgagc agaaacagct gtttgtggaa     3780

cagcacaagc actacctgga cgagatcatc gagcagatca gcgagttctc caagagagtg     3840

atcctggccg acgctaatct ggacaaagtg ctgtccgcct acaacaagca ccgggataag     3900

cccatcagag agcaggccga gaatatcatc cacctgttta ccctgaccaa tctgggagcc     3960

cctgccgcct tcaagtactt tgacaccacc atcgaccgga agaggtacac cagcaccaaa     4020

gaggtgctgg acgccaccct gatccaccag agcatcaccg gcctgtacga gacacggatc     4080

gacctgtctc agctgggagg tgac                                            4104


<210>  44
<211>  1368
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanised amino acid sequence WT Streptococcus pyogenes Cas9

<400>  44

Met Asp Lys Lys Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val 
1               5                   10                  15      


Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe 
            20                  25                  30          


Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile 
        35                  40                  45              


Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 
    50                  55                  60                  


Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 
65                  70                  75                  80  


Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 
                85                  90                  95      


Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 
            100                 105                 110         


His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 
        115                 120                 125             


His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp 
    130                 135                 140                 


Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 
145                 150                 155                 160 


Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro 
                165                 170                 175     


Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 
            180                 185                 190         


Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala 
        195                 200                 205             


Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 
    210                 215                 220                 


Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 
225                 230                 235                 240 


Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe 
                245                 250                 255     


Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 
            260                 265                 270         


Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 
        275                 280                 285             


Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp 
    290                 295                 300                 


Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 
305                 310                 315                 320 


Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 
                325                 330                 335     


Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 
            340                 345                 350         


Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 
        355                 360                 365             


Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 
    370                 375                 380                 


Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg 
385                 390                 395                 400 


Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu 
                405                 410                 415     


Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 
            420                 425                 430         


Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 
        435                 440                 445             


Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 
    450                 455                 460                 


Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 
465                 470                 475                 480 


Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 
                485                 490                 495     


Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 
            500                 505                 510         


Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 
        515                 520                 525             


Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 
    530                 535                 540                 


Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr 
545                 550                 555                 560 


Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 
                565                 570                 575     


Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 
            580                 585                 590         


Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 
        595                 600                 605             


Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 
    610                 615                 620                 


Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 
625                 630                 635                 640 


His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 
                645                 650                 655     


Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 
            660                 665                 670         


Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 
        675                 680                 685             


Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 
    690                 695                 700                 


Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu 
705                 710                 715                 720 


His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly 
                725                 730                 735     


Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly 
            740                 745                 750         


Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln 
        755                 760                 765             


Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile 
    770                 775                 780                 


Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro 
785                 790                 795                 800 


Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu 
                805                 810                 815     


Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg 
            820                 825                 830         


Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys 
        835                 840                 845             


Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg 
    850                 855                 860                 


Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys 
865                 870                 875                 880 


Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys 
                885                 890                 895     


Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp 
            900                 905                 910         


Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr 
        915                 920                 925             


Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp 
    930                 935                 940                 


Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser 
945                 950                 955                 960 


Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg 
                965                 970                 975     


Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val 
            980                 985                 990         


Val Gly Thr Ala Leu Ile Lys Lys  Tyr Pro Lys Leu Glu  Ser Glu Phe 
        995                 1000                 1005             


Val Tyr  Gly Asp Tyr Lys Val  Tyr Asp Val Arg Lys  Met Ile Ala 
    1010                 1015                 1020             


Lys Ser  Glu Gln Glu Ile Gly  Lys Ala Thr Ala Lys  Tyr Phe Phe 
    1025                 1030                 1035             


Tyr Ser  Asn Ile Met Asn Phe  Phe Lys Thr Glu Ile  Thr Leu Ala 
    1040                 1045                 1050             


Asn Gly  Glu Ile Arg Lys Arg  Pro Leu Ile Glu Thr  Asn Gly Glu 
    1055                 1060                 1065             


Thr Gly  Glu Ile Val Trp Asp  Lys Gly Arg Asp Phe  Ala Thr Val 
    1070                 1075                 1080             


Arg Lys  Val Leu Ser Met Pro  Gln Val Asn Ile Val  Lys Lys Thr 
    1085                 1090                 1095             


Glu Val  Gln Thr Gly Gly Phe  Ser Lys Glu Ser Ile  Leu Pro Lys 
    1100                 1105                 1110             


Arg Asn  Ser Asp Lys Leu Ile  Ala Arg Lys Lys Asp  Trp Asp Pro 
    1115                 1120                 1125             


Lys Lys  Tyr Gly Gly Phe Asp  Ser Pro Thr Val Ala  Tyr Ser Val 
    1130                 1135                 1140             


Leu Val  Val Ala Lys Val Glu  Lys Gly Lys Ser Lys  Lys Leu Lys 
    1145                 1150                 1155             


Ser Val  Lys Glu Leu Leu Gly  Ile Thr Ile Met Glu  Arg Ser Ser 
    1160                 1165                 1170             


Phe Glu  Lys Asn Pro Ile Asp  Phe Leu Glu Ala Lys  Gly Tyr Lys 
    1175                 1180                 1185             


Glu Val  Lys Lys Asp Leu Ile  Ile Lys Leu Pro Lys  Tyr Ser Leu 
    1190                 1195                 1200             


Phe Glu  Leu Glu Asn Gly Arg  Lys Arg Met Leu Ala  Ser Ala Gly 
    1205                 1210                 1215             


Glu Leu  Gln Lys Gly Asn Glu  Leu Ala Leu Pro Ser  Lys Tyr Val 
    1220                 1225                 1230             


Asn Phe  Leu Tyr Leu Ala Ser  His Tyr Glu Lys Leu  Lys Gly Ser 
    1235                 1240                 1245             


Pro Glu  Asp Asn Glu Gln Lys  Gln Leu Phe Val Glu  Gln His Lys 
    1250                 1255                 1260             


His Tyr  Leu Asp Glu Ile Ile  Glu Gln Ile Ser Glu  Phe Ser Lys 
    1265                 1270                 1275             


Arg Val  Ile Leu Ala Asp Ala  Asn Leu Asp Lys Val  Leu Ser Ala 
    1280                 1285                 1290             


Tyr Asn  Lys His Arg Asp Lys  Pro Ile Arg Glu Gln  Ala Glu Asn 
    1295                 1300                 1305             


Ile Ile  His Leu Phe Thr Leu  Thr Asn Leu Gly Ala  Pro Ala Ala 
    1310                 1315                 1320             


Phe Lys  Tyr Phe Asp Thr Thr  Ile Asp Arg Lys Arg  Tyr Thr Ser 
    1325                 1330                 1335             


Thr Lys  Glu Val Leu Asp Ala  Thr Leu Ile His Gln  Ser Ile Thr 
    1340                 1345                 1350             


Gly Leu  Tyr Glu Thr Arg Ile  Asp Leu Ser Gln Leu  Gly Gly Asp 
    1355                 1360                 1365             


<210>  45
<211>  4104
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanised nucleotide sequence Streptococcus pyogenes nCas9

<400>  45
atggacaaga agtacagcat cggcctggcc atcggcacca actctgtggg ctgggccgtg       60

atcaccgacg agtacaaggt gcccagcaag aaattcaagg tgctgggcaa caccgaccgg      120

cacagcatca agaagaacct gatcggagcc ctgctgttcg acagcggcga aacagccgag      180

gccacccggc tgaagagaac cgccagaaga agatacacca gacggaagaa ccggatctgc      240

tatctgcaag agatcttcag caacgagatg gccaaggtgg acgacagctt cttccacaga      300

ctggaagagt ccttcctggt ggaagaggat aagaagcacg agcggcaccc catcttcggc      360

aacatcgtgg acgaggtggc ctaccacgag aagtacccca ccatctacca cctgagaaag      420

aaactggtgg acagcaccga caaggccgac ctgcggctga tctatctggc cctggcccac      480

atgatcaagt tccggggcca cttcctgatc gagggcgacc tgaaccccga caacagcgac      540

gtggacaagc tgttcatcca gctggtgcag acctacaacc agctgttcga ggaaaacccc      600

atcaacgcca gcggcgtgga cgccaaggcc atcctgtctg ccagactgag caagagcaga      660

cggctggaaa atctgatcgc ccagctgccc ggcgagaaga agaatggcct gttcggaaac      720

ctgattgccc tgagcctggg cctgaccccc aacttcaaga gcaacttcga cctggccgag      780

gatgccaaac tgcagctgag caaggacacc tacgacgacg acctggacaa cctgctggcc      840

cagatcggcg accagtacgc cgacctgttt ctggccgcca agaacctgtc cgacgccatc      900

ctgctgagcg acatcctgag agtgaacacc gagatcacca aggcccccct gagcgcctct      960

atgatcaaga gatacgacga gcaccaccag gacctgaccc tgctgaaagc tctcgtgcgg     1020

cagcagctgc ctgagaagta caaagagatt ttcttcgacc agagcaagaa cggctacgcc     1080

ggctacattg acggcggagc cagccaggaa gagttctaca agttcatcaa gcccatcctg     1140

gaaaagatgg acggcaccga ggaactgctc gtgaagctga acagagagga cctgctgcgg     1200

aagcagcgga ccttcgacaa cggcagcatc ccccaccaga tccacctggg agagctgcac     1260

gccattctgc ggcggcagga agatttttac ccattcctga aggacaaccg ggaaaagatc     1320

gagaagatcc tgaccttccg catcccctac tacgtgggcc ctctggccag gggaaacagc     1380

agattcgcct ggatgaccag aaagagcgag gaaaccatca ccccctggaa cttcgaggaa     1440

gtggtggaca agggcgcttc cgcccagagc ttcatcgagc ggatgaccaa cttcgataag     1500

aacctgccca acgagaaggt gctgcccaag cacagcctgc tgtacgagta cttcaccgtg     1560

tataacgagc tgaccaaagt gaaatacgtg accgagggaa tgagaaagcc cgccttcctg     1620

agcggcgagc agaaaaaggc catcgtggac ctgctgttca agaccaaccg gaaagtgacc     1680

gtgaagcagc tgaaagagga ctacttcaag aaaatcgagt gcttcgactc cgtggaaatc     1740

tccggcgtgg aagatcggtt caacgcctcc ctgggcacat accacgatct gctgaaaatt     1800

atcaaggaca aggacttcct ggacaatgag gaaaacgagg acattctgga agatatcgtg     1860

ctgaccctga cactgtttga ggacagagag atgatcgagg aacggctgaa aacctatgcc     1920

cacctgttcg acgacaaagt gatgaagcag ctgaagcggc ggagatacac cggctggggc     1980

aggctgagcc ggaagctgat caacggcatc cgggacaagc agtccggcaa gacaatcctg     2040

gatttcctga agtccgacgg cttcgccaac agaaacttca tgcagctgat ccacgacgac     2100

agcctgacct ttaaagagga catccagaaa gcccaggtgt ccggccaggg cgatagcctg     2160

cacgagcaca ttgccaatct ggccggcagc cccgccatta agaagggcat cctgcagaca     2220

gtgaaggtgg tggacgagct cgtgaaagtg atgggccggc acaagcccga gaacatcgtg     2280

atcgaaatgg ccagagagaa ccagaccacc cagaagggac agaagaacag ccgcgagaga     2340

atgaagcgga tcgaagaggg catcaaagag ctgggcagcc agatcctgaa agaacacccc     2400

gtggaaaaca cccagctgca gaacgagaag ctgtacctgt actacctgca gaatgggcgg     2460

gatatgtacg tggaccagga actggacatc aaccggctgt ccgactacga tgtggaccat     2520

atcgtgcctc agagctttct gaaggacgac tccatcgaca acaaggtgct gaccagaagc     2580

gacaagaacc ggggcaagag cgacaacgtg ccctccgaag aggtcgtgaa gaagatgaag     2640

aactactggc ggcagctgct gaacgccaag ctgattaccc agagaaagtt cgacaatctg     2700

accaaggccg agagaggcgg cctgagcgaa ctggataagg ccggcttcat caagagacag     2760

ctggtggaaa cccggcagat cacaaagcac gtggcacaga tcctggactc ccggatgaac     2820

actaagtacg acgagaatga caagctgatc cgggaagtga aagtgatcac cctgaagtcc     2880

aagctggtgt ccgatttccg gaaggatttc cagttttaca aagtgcgcga gatcaacaac     2940

taccaccacg cccacgacgc ctacctgaac gccgtcgtgg gaaccgccct gatcaaaaag     3000

taccctaagc tggaaagcga gttcgtgtac ggcgactaca aggtgtacga cgtgcggaag     3060

atgatcgcca agagcgagca ggaaatcggc aaggctaccg ccaagtactt cttctacagc     3120

aacatcatga actttttcaa gaccgagatt accctggcca acggcgagat ccggaagcgg     3180

cctctgatcg agacaaacgg cgaaaccggg gagatcgtgt gggataaggg ccgggatttt     3240

gccaccgtgc ggaaagtgct gagcatgccc caagtgaata tcgtgaaaaa gaccgaggtg     3300

cagacaggcg gcttcagcaa agagtctatc ctgcccaaga ggaacagcga taagctgatc     3360

gccagaaaga aggactggga ccctaagaag tacggcggct tcgacagccc caccgtggcc     3420

tattctgtgc tggtggtggc caaagtggaa aagggcaagt ccaagaaact gaagagtgtg     3480

aaagagctgc tggggatcac catcatggaa agaagcagct tcgagaagaa tcccatcgac     3540

tttctggaag ccaagggcta caaagaagtg aaaaaggacc tgatcatcaa gctgcctaag     3600

tactccctgt tcgagctgga aaacggccgg aagagaatgc tggcctctgc cggcgaactg     3660

cagaagggaa acgaactggc cctgccctcc aaatatgtga acttcctgta cctggccagc     3720

cactatgaga agctgaaggg ctcccccgag gataatgagc agaaacagct gtttgtggaa     3780

cagcacaagc actacctgga cgagatcatc gagcagatca gcgagttctc caagagagtg     3840

atcctggccg acgctaatct ggacaaagtg ctgtccgcct acaacaagca ccgggataag     3900

cccatcagag agcaggccga gaatatcatc cacctgttta ccctgaccaa tctgggagcc     3960

cctgccgcct tcaagtactt tgacaccacc atcgaccgga agaggtacac cagcaccaaa     4020

gaggtgctgg acgccaccct gatccaccag agcatcaccg gcctgtacga gacacggatc     4080

gacctgtctc agctgggagg tgac                                            4104


<210>  46
<211>  1368
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanised amino acid sequence Streptococcus pyogenes nCas9

<400>  46

Met Asp Lys Lys Tyr Ser Ile Gly Leu Ala Ile Gly Thr Asn Ser Val 
1               5                   10                  15      


Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe 
            20                  25                  30          


Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile 
        35                  40                  45              


Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 
    50                  55                  60                  


Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 
65                  70                  75                  80  


Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 
                85                  90                  95      


Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 
            100                 105                 110         


His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 
        115                 120                 125             


His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp 
    130                 135                 140                 


Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 
145                 150                 155                 160 


Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro 
                165                 170                 175     


Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 
            180                 185                 190         


Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala 
        195                 200                 205             


Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 
    210                 215                 220                 


Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 
225                 230                 235                 240 


Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe 
                245                 250                 255     


Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 
            260                 265                 270         


Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 
        275                 280                 285             


Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp 
    290                 295                 300                 


Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 
305                 310                 315                 320 


Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 
                325                 330                 335     


Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 
            340                 345                 350         


Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 
        355                 360                 365             


Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 
    370                 375                 380                 


Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg 
385                 390                 395                 400 


Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu 
                405                 410                 415     


Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 
            420                 425                 430         


Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 
        435                 440                 445             


Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 
    450                 455                 460                 


Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 
465                 470                 475                 480 


Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 
                485                 490                 495     


Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 
            500                 505                 510         


Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 
        515                 520                 525             


Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 
    530                 535                 540                 


Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr 
545                 550                 555                 560 


Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 
                565                 570                 575     


Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 
            580                 585                 590         


Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 
        595                 600                 605             


Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 
    610                 615                 620                 


Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 
625                 630                 635                 640 


His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 
                645                 650                 655     


Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 
            660                 665                 670         


Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 
        675                 680                 685             


Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 
    690                 695                 700                 


Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu 
705                 710                 715                 720 


His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly 
                725                 730                 735     


Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly 
            740                 745                 750         


Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln 
        755                 760                 765             


Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile 
    770                 775                 780                 


Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro 
785                 790                 795                 800 


Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu 
                805                 810                 815     


Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg 
            820                 825                 830         


Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys 
        835                 840                 845             


Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg 
    850                 855                 860                 


Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys 
865                 870                 875                 880 


Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys 
                885                 890                 895     


Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp 
            900                 905                 910         


Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr 
        915                 920                 925             


Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp 
    930                 935                 940                 


Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser 
945                 950                 955                 960 


Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg 
                965                 970                 975     


Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val 
            980                 985                 990         


Val Gly Thr Ala Leu Ile Lys Lys  Tyr Pro Lys Leu Glu  Ser Glu Phe 
        995                 1000                 1005             


Val Tyr  Gly Asp Tyr Lys Val  Tyr Asp Val Arg Lys  Met Ile Ala 
    1010                 1015                 1020             


Lys Ser  Glu Gln Glu Ile Gly  Lys Ala Thr Ala Lys  Tyr Phe Phe 
    1025                 1030                 1035             


Tyr Ser  Asn Ile Met Asn Phe  Phe Lys Thr Glu Ile  Thr Leu Ala 
    1040                 1045                 1050             


Asn Gly  Glu Ile Arg Lys Arg  Pro Leu Ile Glu Thr  Asn Gly Glu 
    1055                 1060                 1065             


Thr Gly  Glu Ile Val Trp Asp  Lys Gly Arg Asp Phe  Ala Thr Val 
    1070                 1075                 1080             


Arg Lys  Val Leu Ser Met Pro  Gln Val Asn Ile Val  Lys Lys Thr 
    1085                 1090                 1095             


Glu Val  Gln Thr Gly Gly Phe  Ser Lys Glu Ser Ile  Leu Pro Lys 
    1100                 1105                 1110             


Arg Asn  Ser Asp Lys Leu Ile  Ala Arg Lys Lys Asp  Trp Asp Pro 
    1115                 1120                 1125             


Lys Lys  Tyr Gly Gly Phe Asp  Ser Pro Thr Val Ala  Tyr Ser Val 
    1130                 1135                 1140             


Leu Val  Val Ala Lys Val Glu  Lys Gly Lys Ser Lys  Lys Leu Lys 
    1145                 1150                 1155             


Ser Val  Lys Glu Leu Leu Gly  Ile Thr Ile Met Glu  Arg Ser Ser 
    1160                 1165                 1170             


Phe Glu  Lys Asn Pro Ile Asp  Phe Leu Glu Ala Lys  Gly Tyr Lys 
    1175                 1180                 1185             


Glu Val  Lys Lys Asp Leu Ile  Ile Lys Leu Pro Lys  Tyr Ser Leu 
    1190                 1195                 1200             


Phe Glu  Leu Glu Asn Gly Arg  Lys Arg Met Leu Ala  Ser Ala Gly 
    1205                 1210                 1215             


Glu Leu  Gln Lys Gly Asn Glu  Leu Ala Leu Pro Ser  Lys Tyr Val 
    1220                 1225                 1230             


Asn Phe  Leu Tyr Leu Ala Ser  His Tyr Glu Lys Leu  Lys Gly Ser 
    1235                 1240                 1245             


Pro Glu  Asp Asn Glu Gln Lys  Gln Leu Phe Val Glu  Gln His Lys 
    1250                 1255                 1260             


His Tyr  Leu Asp Glu Ile Ile  Glu Gln Ile Ser Glu  Phe Ser Lys 
    1265                 1270                 1275             


Arg Val  Ile Leu Ala Asp Ala  Asn Leu Asp Lys Val  Leu Ser Ala 
    1280                 1285                 1290             


Tyr Asn  Lys His Arg Asp Lys  Pro Ile Arg Glu Gln  Ala Glu Asn 
    1295                 1300                 1305             


Ile Ile  His Leu Phe Thr Leu  Thr Asn Leu Gly Ala  Pro Ala Ala 
    1310                 1315                 1320             


Phe Lys  Tyr Phe Asp Thr Thr  Ile Asp Arg Lys Arg  Tyr Thr Ser 
    1325                 1330                 1335             


Thr Lys  Glu Val Leu Asp Ala  Thr Leu Ile His Gln  Ser Ile Thr 
    1340                 1345                 1350             


Gly Leu  Tyr Glu Thr Arg Ile  Asp Leu Ser Gln Leu  Gly Gly Asp 
    1355                 1360                 1365             


<210>  47
<211>  4104
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanised nucleotide sequence Streptococcus pyogenes dCas9

<400>  47
atggacaaga agtacagcat cggcctggcc atcggcacca actctgtggg ctgggccgtg       60

atcaccgacg agtacaaggt gcccagcaag aaattcaagg tgctgggcaa caccgaccgg      120

cacagcatca agaagaacct gatcggagcc ctgctgttcg acagcggcga aacagccgag      180

gccacccggc tgaagagaac cgccagaaga agatacacca gacggaagaa ccggatctgc      240

tatctgcaag agatcttcag caacgagatg gccaaggtgg acgacagctt cttccacaga      300

ctggaagagt ccttcctggt ggaagaggat aagaagcacg agcggcaccc catcttcggc      360

aacatcgtgg acgaggtggc ctaccacgag aagtacccca ccatctacca cctgagaaag      420

aaactggtgg acagcaccga caaggccgac ctgcggctga tctatctggc cctggcccac      480

atgatcaagt tccggggcca cttcctgatc gagggcgacc tgaaccccga caacagcgac      540

gtggacaagc tgttcatcca gctggtgcag acctacaacc agctgttcga ggaaaacccc      600

atcaacgcca gcggcgtgga cgccaaggcc atcctgtctg ccagactgag caagagcaga      660

cggctggaaa atctgatcgc ccagctgccc ggcgagaaga agaatggcct gttcggaaac      720

ctgattgccc tgagcctggg cctgaccccc aacttcaaga gcaacttcga cctggccgag      780

gatgccaaac tgcagctgag caaggacacc tacgacgacg acctggacaa cctgctggcc      840

cagatcggcg accagtacgc cgacctgttt ctggccgcca agaacctgtc cgacgccatc      900

ctgctgagcg acatcctgag agtgaacacc gagatcacca aggcccccct gagcgcctct      960

atgatcaaga gatacgacga gcaccaccag gacctgaccc tgctgaaagc tctcgtgcgg     1020

cagcagctgc ctgagaagta caaagagatt ttcttcgacc agagcaagaa cggctacgcc     1080

ggctacattg acggcggagc cagccaggaa gagttctaca agttcatcaa gcccatcctg     1140

gaaaagatgg acggcaccga ggaactgctc gtgaagctga acagagagga cctgctgcgg     1200

aagcagcgga ccttcgacaa cggcagcatc ccccaccaga tccacctggg agagctgcac     1260

gccattctgc ggcggcagga agatttttac ccattcctga aggacaaccg ggaaaagatc     1320

gagaagatcc tgaccttccg catcccctac tacgtgggcc ctctggccag gggaaacagc     1380

agattcgcct ggatgaccag aaagagcgag gaaaccatca ccccctggaa cttcgaggaa     1440

gtggtggaca agggcgcttc cgcccagagc ttcatcgagc ggatgaccaa cttcgataag     1500

aacctgccca acgagaaggt gctgcccaag cacagcctgc tgtacgagta cttcaccgtg     1560

tataacgagc tgaccaaagt gaaatacgtg accgagggaa tgagaaagcc cgccttcctg     1620

agcggcgagc agaaaaaggc catcgtggac ctgctgttca agaccaaccg gaaagtgacc     1680

gtgaagcagc tgaaagagga ctacttcaag aaaatcgagt gcttcgactc cgtggaaatc     1740

tccggcgtgg aagatcggtt caacgcctcc ctgggcacat accacgatct gctgaaaatt     1800

atcaaggaca aggacttcct ggacaatgag gaaaacgagg acattctgga agatatcgtg     1860

ctgaccctga cactgtttga ggacagagag atgatcgagg aacggctgaa aacctatgcc     1920

cacctgttcg acgacaaagt gatgaagcag ctgaagcggc ggagatacac cggctggggc     1980

aggctgagcc ggaagctgat caacggcatc cgggacaagc agtccggcaa gacaatcctg     2040

gatttcctga agtccgacgg cttcgccaac agaaacttca tgcagctgat ccacgacgac     2100

agcctgacct ttaaagagga catccagaaa gcccaggtgt ccggccaggg cgatagcctg     2160

cacgagcaca ttgccaatct ggccggcagc cccgccatta agaagggcat cctgcagaca     2220

gtgaaggtgg tggacgagct cgtgaaagtg atgggccggc acaagcccga gaacatcgtg     2280

atcgaaatgg ccagagagaa ccagaccacc cagaagggac agaagaacag ccgcgagaga     2340

atgaagcgga tcgaagaggg catcaaagag ctgggcagcc agatcctgaa agaacacccc     2400

gtggaaaaca cccagctgca gaacgagaag ctgtacctgt actacctgca gaatgggcgg     2460

gatatgtacg tggaccagga actggacatc aaccggctgt ccgactacga tgtggacgct     2520

atcgtgcctc agagctttct gaaggacgac tccatcgaca acaaggtgct gaccagaagc     2580

gacaagaacc ggggcaagag cgacaacgtg ccctccgaag aggtcgtgaa gaagatgaag     2640

aactactggc ggcagctgct gaacgccaag ctgattaccc agagaaagtt cgacaatctg     2700

accaaggccg agagaggcgg cctgagcgaa ctggataagg ccggcttcat caagagacag     2760

ctggtggaaa cccggcagat cacaaagcac gtggcacaga tcctggactc ccggatgaac     2820

actaagtacg acgagaatga caagctgatc cgggaagtga aagtgatcac cctgaagtcc     2880

aagctggtgt ccgatttccg gaaggatttc cagttttaca aagtgcgcga gatcaacaac     2940

taccaccacg cccacgacgc ctacctgaac gccgtcgtgg gaaccgccct gatcaaaaag     3000

taccctaagc tggaaagcga gttcgtgtac ggcgactaca aggtgtacga cgtgcggaag     3060

atgatcgcca agagcgagca ggaaatcggc aaggctaccg ccaagtactt cttctacagc     3120

aacatcatga actttttcaa gaccgagatt accctggcca acggcgagat ccggaagcgg     3180

cctctgatcg agacaaacgg cgaaaccggg gagatcgtgt gggataaggg ccgggatttt     3240

gccaccgtgc ggaaagtgct gagcatgccc caagtgaata tcgtgaaaaa gaccgaggtg     3300

cagacaggcg gcttcagcaa agagtctatc ctgcccaaga ggaacagcga taagctgatc     3360

gccagaaaga aggactggga ccctaagaag tacggcggct tcgacagccc caccgtggcc     3420

tattctgtgc tggtggtggc caaagtggaa aagggcaagt ccaagaaact gaagagtgtg     3480

aaagagctgc tggggatcac catcatggaa agaagcagct tcgagaagaa tcccatcgac     3540

tttctggaag ccaagggcta caaagaagtg aaaaaggacc tgatcatcaa gctgcctaag     3600

tactccctgt tcgagctgga aaacggccgg aagagaatgc tggcctctgc cggcgaactg     3660

cagaagggaa acgaactggc cctgccctcc aaatatgtga acttcctgta cctggccagc     3720

cactatgaga agctgaaggg ctcccccgag gataatgagc agaaacagct gtttgtggaa     3780

cagcacaagc actacctgga cgagatcatc gagcagatca gcgagttctc caagagagtg     3840

atcctggccg acgctaatct ggacaaagtg ctgtccgcct acaacaagca ccgggataag     3900

cccatcagag agcaggccga gaatatcatc cacctgttta ccctgaccaa tctgggagcc     3960

cctgccgcct tcaagtactt tgacaccacc atcgaccgga agaggtacac cagcaccaaa     4020

gaggtgctgg acgccaccct gatccaccag agcatcaccg gcctgtacga gacacggatc     4080

gacctgtctc agctgggagg tgac                                            4104


<210>  48
<211>  1229
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence WT AsCas12a

<400>  48

Ala Ile Asp Ser Tyr Arg Lys Glu Lys Thr Glu Glu Thr Arg Asn Ala 
1               5                   10                  15      


Leu Ile Glu Glu Gln Ala Thr Tyr Arg Asn Ala Ile His Asp Tyr Phe 
            20                  25                  30          


Ile Gly Arg Thr Asp Asn Leu Thr Asp Ala Ile Asn Lys Arg His Ala 
        35                  40                  45              


Glu Ile Tyr Lys Gly Leu Phe Lys Ala Glu Leu Phe Asn Gly Lys Val 
    50                  55                  60                  


Leu Lys Gln Leu Gly Thr Val Thr Thr Thr Glu His Glu Asn Ala Leu 
65                  70                  75                  80  


Leu Arg Ser Phe Asp Lys Phe Thr Thr Tyr Phe Ser Gly Phe Tyr Glu 
                85                  90                  95      


Asn Arg Lys Asn Val Phe Ser Ala Glu Asp Ile Ser Thr Ala Ile Pro 
            100                 105                 110         


His Arg Ile Val Gln Asp Asn Phe Pro Lys Phe Lys Glu Asn Cys His 
        115                 120                 125             


Ile Phe Thr Arg Leu Ile Thr Ala Val Pro Ser Leu Arg Glu His Phe 
    130                 135                 140                 


Glu Asn Val Lys Lys Ala Ile Gly Ile Phe Val Ser Thr Ser Ile Glu 
145                 150                 155                 160 


Glu Val Phe Ser Phe Pro Phe Tyr Asn Gln Leu Leu Thr Gln Thr Gln 
                165                 170                 175     


Ile Asp Leu Tyr Asn Gln Leu Leu Gly Gly Ile Ser Arg Glu Ala Gly 
            180                 185                 190         


Thr Glu Lys Ile Lys Gly Leu Asn Glu Val Leu Asn Leu Ala Ile Gln 
        195                 200                 205             


Lys Asn Asp Glu Thr Ala His Ile Ile Ala Ser Leu Pro His Arg Phe 
    210                 215                 220                 


Ile Pro Leu Phe Lys Gln Ile Leu Ser Asp Arg Asn Thr Leu Ser Phe 
225                 230                 235                 240 


Ile Leu Glu Glu Phe Lys Ser Asp Glu Glu Val Ile Gln Ser Phe Cys 
                245                 250                 255     


Lys Tyr Lys Thr Leu Leu Arg Asn Glu Asn Val Leu Glu Thr Ala Glu 
            260                 265                 270         


Ala Leu Phe Asn Glu Leu Asn Ser Ile Asp Leu Thr His Ile Phe Ile 
        275                 280                 285             


Ser His Lys Lys Leu Glu Thr Ile Ser Ser Ala Leu Cys Asp His Trp 
    290                 295                 300                 


Asp Thr Leu Arg Asn Ala Leu Tyr Glu Arg Arg Ile Ser Glu Leu Thr 
305                 310                 315                 320 


Gly Lys Ile Thr Lys Ser Ala Lys Glu Lys Val Gln Arg Ser Leu Lys 
                325                 330                 335     


His Glu Asp Ile Asn Leu Gln Glu Ile Ile Ser Ala Ala Gly Lys Glu 
            340                 345                 350         


Leu Ser Glu Ala Phe Lys Gln Lys Thr Ser Glu Ile Leu Ser His Ala 
        355                 360                 365             


His Ala Ala Leu Asp Gln Pro Leu Pro Thr Thr Leu Lys Lys Gln Glu 
    370                 375                 380                 


Glu Lys Glu Ile Leu Lys Ser Gln Leu Asp Ser Leu Leu Gly Leu Tyr 
385                 390                 395                 400 


His Leu Leu Asp Trp Phe Ala Val Asp Glu Ser Asn Glu Val Asp Pro 
                405                 410                 415     


Glu Phe Ser Ala Arg Leu Thr Gly Ile Lys Leu Glu Met Glu Pro Ser 
            420                 425                 430         


Leu Ser Phe Tyr Asn Lys Ala Arg Asn Tyr Ala Thr Lys Lys Pro Tyr 
        435                 440                 445             


Ser Val Glu Lys Phe Lys Leu Asn Phe Gln Met Pro Thr Leu Ala Ser 
    450                 455                 460                 


Gly Trp Asp Val Asn Lys Glu Lys Asn Asn Gly Ala Ile Leu Phe Val 
465                 470                 475                 480 


Lys Asn Gly Leu Tyr Tyr Leu Gly Ile Met Pro Lys Gln Lys Gly Arg 
                485                 490                 495     


Tyr Lys Ala Leu Ser Phe Glu Pro Thr Glu Lys Thr Ser Glu Gly Phe 
            500                 505                 510         


Asp Lys Met Tyr Tyr Asp Tyr Phe Pro Asp Ala Ala Lys Met Ile Pro 
        515                 520                 525             


Lys Cys Ser Thr Gln Leu Lys Ala Val Thr Ala His Phe Gln Thr His 
    530                 535                 540                 


Thr Thr Pro Ile Leu Leu Ser Asn Asn Phe Ile Glu Pro Leu Glu Ile 
545                 550                 555                 560 


Thr Lys Glu Ile Tyr Asp Leu Asn Asn Pro Glu Lys Glu Pro Lys Lys 
                565                 570                 575     


Phe Gln Thr Ala Tyr Ala Lys Lys Thr Gly Asp Gln Lys Gly Tyr Arg 
            580                 585                 590         


Glu Ala Leu Cys Lys Trp Ile Asp Phe Thr Arg Asp Phe Leu Ser Lys 
        595                 600                 605             


Tyr Thr Lys Thr Thr Ser Ile Asp Leu Ser Ser Leu Arg Pro Ser Ser 
    610                 615                 620                 


Gln Tyr Lys Asp Leu Gly Glu Tyr Tyr Ala Glu Leu Asn Pro Leu Leu 
625                 630                 635                 640 


Tyr His Ile Ser Phe Gln Arg Ile Ala Glu Lys Glu Ile Met Asp Ala 
                645                 650                 655     


Val Glu Thr Gly Lys Leu Tyr Leu Phe Gln Ile Tyr Asn Lys Asp Phe 
            660                 665                 670         


Ala Lys Gly His His Gly Lys Pro Asn Leu His Thr Leu Tyr Trp Thr 
        675                 680                 685             


Gly Leu Phe Ser Pro Glu Asn Leu Ala Lys Thr Ser Ile Lys Leu Asn 
    690                 695                 700                 


Gly Gln Ala Glu Leu Phe Tyr Arg Pro Lys Ser Arg Met Lys Arg Met 
705                 710                 715                 720 


Ala His Arg Leu Gly Glu Lys Met Leu Asn Lys Lys Leu Lys Asp Gln 
                725                 730                 735     


Lys Thr Pro Ile Pro Asp Thr Leu Tyr Gln Glu Leu Tyr Asp Tyr Val 
            740                 745                 750         


Asn His Arg Leu Ser His Asp Leu Ser Asp Glu Ala Arg Ala Leu Leu 
        755                 760                 765             


Pro Asn Val Ile Thr Lys Glu Val Ser His Glu Ile Ile Lys Asp Arg 
    770                 775                 780                 


Arg Phe Thr Ser Asp Lys Phe Phe Phe His Val Pro Ile Thr Leu Asn 
785                 790                 795                 800 


Tyr Gln Ala Ala Asn Ser Pro Ser Lys Phe Asn Gln Arg Val Asn Ala 
                805                 810                 815     


Tyr Leu Lys Glu His Pro Glu Thr Pro Ile Ile Gly Ile Asp Arg Gly 
            820                 825                 830         


Glu Arg Asn Leu Ile Tyr Ile Thr Val Ile Asp Ser Thr Gly Lys Ile 
        835                 840                 845             


Leu Glu Gln Arg Ser Leu Asn Thr Ile Gln Gln Phe Asp Tyr Gln Lys 
    850                 855                 860                 


Lys Leu Asp Asn Arg Glu Lys Glu Arg Val Ala Ala Arg Gln Ala Trp 
865                 870                 875                 880 


Ser Val Val Gly Thr Ile Lys Asp Leu Lys Gln Gly Tyr Leu Ser Gln 
                885                 890                 895     


Val Ile His Glu Ile Val Asp Leu Met Ile His Tyr Gln Ala Val Val 
            900                 905                 910         


Val Leu Glu Asn Leu Asn Phe Gly Phe Lys Ser Lys Arg Thr Gly Ile 
        915                 920                 925             


Ala Glu Lys Ala Val Tyr Gln Gln Phe Glu Lys Met Leu Ile Asp Lys 
    930                 935                 940                 


Leu Asn Cys Leu Val Leu Lys Asp Tyr Pro Ala Glu Lys Val Gly Gly 
945                 950                 955                 960 


Val Leu Asn Pro Tyr Gln Leu Thr Asp Gln Phe Thr Ser Phe Ala Lys 
                965                 970                 975     


Met Gly Thr Gln Ser Gly Phe Leu Phe Tyr Val Pro Ala Pro Tyr Thr 
            980                 985                 990         


Ser Lys Ile Asp Pro Leu Thr Gly  Phe Val Asp Pro Phe  Val Trp Lys 
        995                 1000                 1005             


Thr Ile  Lys Asn His Glu Ser  Arg Lys His Phe Leu  Glu Gly Phe 
    1010                 1015                 1020             


Asp Phe  Leu His Tyr Asp Val  Lys Thr Gly Asp Phe  Ile Leu His 
    1025                 1030                 1035             


Phe Lys  Met Asn Arg Asn Leu  Ser Phe Gln Arg Gly  Leu Pro Gly 
    1040                 1045                 1050             


Phe Met  Pro Ala Trp Asp Ile  Val Phe Glu Lys Asn  Glu Thr Gln 
    1055                 1060                 1065             


Phe Asp  Ala Lys Gly Thr Pro  Phe Ile Ala Gly Lys  Arg Ile Val 
    1070                 1075                 1080             


Pro Val  Ile Glu Asn His Arg  Phe Thr Gly Arg Tyr  Arg Asp Leu 
    1085                 1090                 1095             


Tyr Pro  Ala Asn Glu Leu Ile  Ala Leu Leu Glu Glu  Lys Gly Ile 
    1100                 1105                 1110             


Val Phe  Arg Asp Gly Ser Asn  Ile Leu Pro Lys Leu  Leu Glu Asn 
    1115                 1120                 1125             


Asp Asp  Ser His Ala Ile Asp  Thr Met Val Ala Leu  Ile Arg Ser 
    1130                 1135                 1140             


Val Leu  Gln Met Arg Asn Ser  Asn Ala Ala Thr Gly  Glu Asp Tyr 
    1145                 1150                 1155             


Ile Asn  Ser Pro Val Arg Asp  Leu Asn Gly Val Cys  Phe Asp Ser 
    1160                 1165                 1170             


Arg Phe  Gln Asn Pro Glu Trp  Pro Met Asp Ala Asp  Ala Asn Gly 
    1175                 1180                 1185             


Ala Tyr  His Ile Ala Leu Lys  Gly Gln Leu Leu Leu  Asn His Leu 
    1190                 1195                 1200             


Lys Glu  Ser Lys Asp Leu Lys  Leu Gln Asn Gly Ile  Ser Asn Gln 
    1205                 1210                 1215             


Asp Trp  Leu Ala Tyr Ile Gln  Glu Leu Arg Asn 
    1220                 1225                 


<210>  49
<211>  1129
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence WT AaCas12b

<400>  49

Met Ala Val Lys Ser Met Lys Val Lys Leu Arg Leu Asp Asn Met Pro 
1               5                   10                  15      


Glu Ile Arg Ala Gly Leu Trp Lys Leu His Thr Glu Val Asn Ala Gly 
            20                  25                  30          


Val Arg Tyr Tyr Thr Glu Trp Leu Ser Leu Leu Arg Gln Glu Asn Leu 
        35                  40                  45              


Tyr Arg Arg Ser Pro Asn Gly Asp Gly Glu Gln Glu Cys Tyr Lys Thr 
    50                  55                  60                  


Ala Glu Glu Cys Lys Ala Glu Leu Leu Glu Arg Leu Arg Ala Arg Gln 
65                  70                  75                  80  


Val Glu Asn Gly His Cys Gly Pro Ala Gly Ser Asp Asp Glu Leu Leu 
                85                  90                  95      


Gln Leu Ala Arg Gln Leu Tyr Glu Leu Leu Val Pro Gln Ala Ile Gly 
            100                 105                 110         


Ala Lys Gly Asp Ala Gln Gln Ile Ala Arg Lys Phe Leu Ser Pro Leu 
        115                 120                 125             


Ala Asp Lys Asp Ala Val Gly Gly Leu Gly Ile Ala Lys Ala Gly Asn 
    130                 135                 140                 


Lys Pro Arg Trp Val Arg Met Arg Glu Ala Gly Glu Pro Gly Trp Glu 
145                 150                 155                 160 


Glu Glu Lys Ala Lys Ala Glu Ala Arg Lys Ser Thr Asp Arg Thr Ala 
                165                 170                 175     


Asp Val Leu Arg Ala Leu Ala Asp Phe Gly Leu Lys Pro Leu Met Arg 
            180                 185                 190         


Val Tyr Thr Asp Ser Asp Met Ser Ser Val Gln Trp Lys Pro Leu Arg 
        195                 200                 205             


Lys Gly Gln Ala Val Arg Thr Trp Asp Arg Asp Met Phe Gln Gln Ala 
    210                 215                 220                 


Ile Glu Arg Met Met Ser Trp Glu Ser Trp Asn Gln Arg Val Gly Glu 
225                 230                 235                 240 


Ala Tyr Ala Lys Leu Val Glu Gln Lys Ser Arg Phe Glu Gln Lys Asn 
                245                 250                 255     


Phe Val Gly Gln Glu His Leu Val Gln Leu Val Asn Gln Leu Gln Gln 
            260                 265                 270         


Asp Met Lys Glu Ala Ser His Gly Leu Glu Ser Lys Glu Gln Thr Ala 
        275                 280                 285             


His Tyr Leu Thr Gly Arg Ala Leu Arg Gly Ser Asp Lys Val Phe Glu 
    290                 295                 300                 


Lys Trp Glu Lys Leu Asp Pro Asp Ala Pro Phe Asp Leu Tyr Asp Thr 
305                 310                 315                 320 


Glu Ile Lys Asn Val Gln Arg Arg Asn Thr Arg Arg Phe Gly Ser His 
                325                 330                 335     


Asp Leu Phe Ala Lys Leu Ala Glu Pro Lys Tyr Gln Ala Leu Trp Arg 
            340                 345                 350         


Glu Asp Ala Ser Phe Leu Thr Arg Tyr Ala Val Tyr Asn Ser Ile Val 
        355                 360                 365             


Arg Lys Leu Asn His Ala Lys Met Phe Ala Thr Phe Thr Leu Pro Asp 
    370                 375                 380                 


Ala Thr Ala His Pro Ile Trp Thr Arg Phe Asp Lys Leu Gly Gly Asn 
385                 390                 395                 400 


Leu His Gln Tyr Thr Phe Leu Phe Asn Glu Phe Gly Glu Gly Arg His 
                405                 410                 415     


Ala Ile Arg Phe Gln Lys Leu Leu Thr Val Glu Asp Gly Val Ala Lys 
            420                 425                 430         


Glu Val Asp Asp Val Thr Val Pro Ile Ser Met Ser Ala Gln Leu Asp 
        435                 440                 445             


Asp Leu Leu Pro Arg Asp Pro His Glu Leu Val Ala Leu Tyr Phe Gln 
    450                 455                 460                 


Asp Tyr Gly Ala Glu Gln His Leu Ala Gly Glu Phe Gly Gly Ala Lys 
465                 470                 475                 480 


Ile Gln Tyr Arg Arg Asp Gln Leu Asn His Leu His Ala Arg Arg Gly 
                485                 490                 495     


Ala Arg Asp Val Tyr Leu Asn Leu Ser Val Arg Val Gln Ser Gln Ser 
            500                 505                 510         


Glu Ala Arg Gly Glu Arg Arg Pro Pro Tyr Ala Ala Val Phe Arg Leu 
        515                 520                 525             


Val Gly Asp Asn His Arg Ala Phe Val His Phe Asp Lys Leu Ser Asp 
    530                 535                 540                 


Tyr Leu Ala Glu His Pro Asp Asp Gly Lys Leu Gly Ser Glu Gly Leu 
545                 550                 555                 560 


Leu Ser Gly Leu Arg Val Met Ser Val Asp Leu Gly Leu Arg Thr Ser 
                565                 570                 575     


Ala Ser Ile Ser Val Phe Arg Val Ala Arg Lys Asp Glu Leu Lys Pro 
            580                 585                 590         


Asn Ser Glu Gly Arg Val Pro Phe Cys Phe Pro Ile Glu Gly Asn Glu 
        595                 600                 605             


Asn Leu Val Ala Val His Glu Arg Ser Gln Leu Leu Lys Leu Pro Gly 
    610                 615                 620                 


Glu Thr Glu Ser Lys Asp Leu Arg Ala Ile Arg Glu Glu Arg Gln Arg 
625                 630                 635                 640 


Thr Leu Arg Gln Leu Arg Thr Gln Leu Ala Tyr Leu Arg Leu Leu Val 
                645                 650                 655     


Arg Cys Gly Ser Glu Asp Val Gly Arg Arg Glu Arg Ser Trp Ala Lys 
            660                 665                 670         


Leu Ile Glu Gln Pro Met Asp Ala Asn Gln Met Thr Pro Asp Trp Arg 
        675                 680                 685             


Glu Ala Phe Glu Asp Glu Leu Gln Lys Leu Lys Ser Leu Tyr Gly Ile 
    690                 695                 700                 


Cys Gly Asp Arg Glu Trp Thr Glu Ala Val Tyr Glu Ser Val Arg Arg 
705                 710                 715                 720 


Val Trp Arg His Met Gly Lys Gln Val Arg Asp Trp Arg Lys Asp Val 
                725                 730                 735     


Arg Ser Gly Glu Arg Pro Lys Ile Arg Gly Tyr Gln Lys Asp Val Val 
            740                 745                 750         


Gly Gly Asn Ser Ile Glu Gln Ile Glu Tyr Leu Glu Arg Gln Tyr Lys 
        755                 760                 765             


Phe Leu Lys Ser Trp Ser Phe Phe Gly Lys Val Ser Gly Gln Val Ile 
    770                 775                 780                 


Arg Ala Glu Lys Gly Ser Arg Phe Ala Ile Thr Leu Arg Glu His Ile 
785                 790                 795                 800 


Asp His Ala Lys Glu Asp Arg Leu Lys Lys Leu Ala Asp Arg Ile Ile 
                805                 810                 815     


Met Glu Ala Leu Gly Tyr Val Tyr Ala Leu Asp Asp Glu Arg Gly Lys 
            820                 825                 830         


Gly Lys Trp Val Ala Lys Tyr Pro Pro Cys Gln Leu Ile Leu Leu Glu 
        835                 840                 845             


Glu Leu Ser Glu Tyr Gln Phe Asn Asn Asp Arg Pro Pro Ser Glu Asn 
    850                 855                 860                 


Asn Gln Leu Met Gln Trp Ser His Arg Gly Val Phe Gln Glu Leu Leu 
865                 870                 875                 880 


Asn Gln Ala Gln Val His Asp Leu Leu Val Gly Thr Met Tyr Ala Ala 
                885                 890                 895     


Phe Ser Ser Arg Phe Asp Ala Arg Thr Gly Ala Pro Gly Ile Arg Cys 
            900                 905                 910         


Arg Arg Val Pro Ala Arg Cys Ala Arg Glu Gln Asn Pro Glu Pro Phe 
        915                 920                 925             


Pro Trp Trp Leu Asn Lys Phe Val Ala Glu His Lys Leu Asp Gly Cys 
    930                 935                 940                 


Pro Leu Arg Ala Asp Asp Leu Ile Pro Thr Gly Glu Gly Glu Phe Phe 
945                 950                 955                 960 


Val Ser Pro Phe Ser Ala Glu Glu Gly Asp Phe His Gln Ile His Ala 
                965                 970                 975     


Asp Leu Asn Ala Ala Gln Asn Leu Gln Arg Arg Leu Trp Ser Asp Phe 
            980                 985                 990         


Asp Ile Ser Gln Ile Arg Leu Arg  Cys Asp Trp Gly Glu  Val Asp Gly 
        995                 1000                 1005             


Glu Pro  Val Leu Ile Pro Arg  Thr Thr Gly Lys Arg  Thr Ala Asp 
    1010                 1015                 1020             


Ser Tyr  Gly Asn Lys Val Phe  Tyr Thr Lys Thr Gly  Val Thr Tyr 
    1025                 1030                 1035             


Tyr Glu  Arg Glu Arg Gly Lys  Lys Arg Arg Lys Val  Phe Ala Gln 
    1040                 1045                 1050             


Glu Glu  Leu Ser Glu Glu Glu  Ala Glu Leu Leu Val  Glu Ala Asp 
    1055                 1060                 1065             


Glu Ala  Arg Glu Lys Ser Val  Val Leu Met Arg Asp  Pro Ser Gly 
    1070                 1075                 1080             


Ile Ile  Asn Arg Gly Asp Trp  Thr Arg Gln Lys Glu  Phe Trp Ser 
    1085                 1090                 1095             


Met Val  Asn Gln Arg Ile Glu  Gly Tyr Leu Val Lys  Gln Ile Arg 
    1100                 1105                 1110             


Ser Arg  Val Arg Leu Gln Glu  Ser Ala Cys Glu Asn  Thr Gly Asp 
    1115                 1120                 1125             


Ile 
    


<210>  50
<211>  1258
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence WT Cas12d1

<400>  50

Met Asn Glu Lys Lys Thr Ala Thr Gln Arg Arg Asn Ala Arg Arg Arg 
1               5                   10                  15      


Arg Gly Glu Arg Ala Arg Thr Lys Ser Gln Glu Leu Arg Gly Tyr Arg 
            20                  25                  30          


Leu His Asp Ala Arg Ile Glu Phe Ser Gly Gly Leu Gly Ser Met Arg 
        35                  40                  45              


Thr Val Lys Val Glu Leu Leu Asn Pro Asp Ser Ser Arg Glu Asp Pro 
    50                  55                  60                  


Gln Arg Gly Gln Gly Leu Gln Gly Lys Val Ala Lys Ala Val Phe Asp 
65                  70                  75                  80  


Asp Tyr Arg Ala Leu Tyr Gly Pro Met Asn Ile Glu Asp Tyr Leu Ser 
                85                  90                  95      


Asp Pro Asp Cys Pro Ser Phe Leu Gly Leu Trp Val Lys Ala Val Cys 
            100                 105                 110         


Leu Gly Val Ile Met Ser Arg Lys Thr Ala Thr Asp Phe Gly Glu Leu 
        115                 120                 125             


Arg Gly Gly Ser Lys Ser Gly Gln Ala Phe Asp Ser Ile Pro Glu His 
    130                 135                 140                 


Leu Arg Arg Gln Leu Ile Lys Leu Lys Trp Leu Asp Trp Tyr Asp Lys 
145                 150                 155                 160 


Gly Ile Arg Lys Ser Ser Ser Lys Ala Ser Arg Leu Lys Ser Leu Thr 
                165                 170                 175     


Asp Val Phe Ala Asn Pro Lys Gln Pro Asp Gln Gly Val Met Ala Ala 
            180                 185                 190         


Trp Glu Gln Gly Glu Lys Leu Ala Glu Ser Ser Arg Asp Ile Ala Ala 
        195                 200                 205             


Leu Gly Arg Arg Glu Phe Lys Asp Lys Leu Phe Ala Ile Pro Pro Pro 
    210                 215                 220                 


Thr Ser Ser Val Val Leu Asp Asp Asp Val Lys Ala Thr Lys Val Ser 
225                 230                 235                 240 


Arg Asp Trp Gln Trp Ala Val Asp Pro Gln Phe Lys Leu Pro Ser Thr 
                245                 250                 255     


Asp Leu Asp Ile Thr Arg Ala Leu Glu Glu Val Asp Arg Gln Trp Phe 
            260                 265                 270         


Glu Arg Leu Gly Asn Asn Arg Gly Met Val Gln Gln Phe Phe Ala Ile 
        275                 280                 285             


Gly Asp Asn Gly Asn His Leu Asn Asn Gly Leu Phe Gly His Phe Phe 
    290                 295                 300                 


Ala Ser Ile Arg Ser Ala Asn Leu Ala Asp Ile Val Ala Glu Met Gly 
305                 310                 315                 320 


Thr Ala Phe Gly Phe Ser Ala Glu Glu Arg Asp Ile Val Arg Gln Arg 
                325                 330                 335     


Leu Glu Thr Leu His Glu Tyr Ala Gln Gly Leu Pro Glu Lys Pro Val 
            340                 345                 350         


Leu Ala Ser Arg Trp Ala Glu Tyr Arg Thr Asp Met Thr Ala Lys Leu 
        355                 360                 365             


Gly Ser Trp Tyr Ser Asn Arg Thr Ser Lys Gly Ala Ala Ser Ile Thr 
    370                 375                 380                 


Gln Val Trp Gly Thr Ile Asn Thr Glu Thr Gly Glu Val Lys Asp Asp 
385                 390                 395                 400 


Gly Leu Val Arg Thr Leu Glu Asn Ile Gln Ser Asp Leu Pro Asp Ser 
                405                 410                 415     


Cys Ser Ile Lys Glu Gly Ile Leu Gln Glu Thr Leu Asp Phe Ile Gly 
            420                 425                 430         


Asp Arg Arg Ser Ser Thr Asp Arg Ala Phe Thr Asp Glu Leu Glu Leu 
        435                 440                 445             


Tyr Leu Ala Thr Leu Arg Ser Asp Leu Asn Thr Trp Cys Gln Glu Gln 
    450                 455                 460                 


Ser Ala Leu Trp Glu Glu Lys Gln Arg Gln Val Ala Thr Pro Ala Ser 
465                 470                 475                 480 


Asp Glu Lys Ser Lys Lys Ala Asp Asn Pro Trp Ala Gly Lys Gly Ser 
                485                 490                 495     


Lys Thr Asp Lys Trp Leu Gly Ala Leu His Thr Arg Ile Gln Ser Ser 
            500                 505                 510         


Pro Leu Phe Trp Gly Val Asp Lys Leu Glu Leu Trp Lys Thr Leu Ala 
        515                 520                 525             


Asn Leu Lys Gln Ala Ile Arg Asp Glu Ile Asp Lys Leu Asn Glu Gln 
    530                 535                 540                 


Val Glu Val Phe Gly Arg Ser Ala Tyr Asp Glu Pro Val Gly Lys Asp 
545                 550                 555                 560 


Ala Asp Ser Gly Glu Gly Asp Arg Arg Val Asp Gln Leu Ser Tyr Leu 
                565                 570                 575     


Ser Ala Arg Leu Gly Asp Gln Ala His Glu Glu Val Arg Gln Arg Leu 
            580                 585                 590         


Asp Ala Ile Ala Leu Ala Leu Gly Val Lys Phe Ser Glu Arg Asp Asp 
        595                 600                 605             


Leu His Arg Phe Phe Val Ser Ser Arg Ala Arg Arg Arg Ala Ala Leu 
    610                 615                 620                 


Leu Ala Met Pro Asn Thr Ile Thr Val Gly Lys Leu Arg Glu Leu Ala 
625                 630                 635                 640 


Asp Leu Thr Pro Leu Trp Glu Arg Ile Lys Lys Lys Pro Glu Glu Pro 
                645                 650                 655     


Arg Leu Leu Ala Asp Thr Val Ala Leu Ser Lys Val Val Asn Ser Ala 
            660                 665                 670         


Cys Ala Ser Arg Ala Asn Pro Ser Asp Gln Ile Glu Leu Thr Thr Ile 
        675                 680                 685             


His Ser Arg Leu Asp Gly Tyr Ser Lys Asn Ile Gly His Thr Glu Phe 
    690                 695                 700                 


Ile Ser Arg Ala Thr Val Gln Ser Thr Asn Gly Ala Gln Asn Thr Val 
705                 710                 715                 720 


Ala Leu Asp Ser Leu Val Ser Pro Arg Leu Phe Tyr Tyr Asn Phe Pro 
                725                 730                 735     


Asn Ile Val Glu Ser Ala Glu Pro His Val Ser His Leu Glu Val Ala 
            740                 745                 750         


Thr Arg Gly Asn Leu Gly Ser Phe Glu Glu Phe Ala Ala Lys Glu His 
        755                 760                 765             


Arg Thr Phe Asp Arg Glu Asn Pro Gln Lys Asp Ser Arg Asn Arg Ile 
    770                 775                 780                 


Asp Ser Val Asn Pro Leu Ala Val Ala Ser Ser Arg Tyr Gln Ile Gln 
785                 790                 795                 800 


Phe Phe Thr Trp Trp Ala Gly Leu His Arg Ser Lys Glu Thr Ala Leu 
                805                 810                 815     


Glu Val Gly Gly Ser Phe Thr Ile Ala Glu Arg Gln Val Arg Leu Asp 
            820                 825                 830         


Trp Ser Gln Glu Lys Pro Gln Ala Val Val Ser Glu Glu Leu Arg Val 
        835                 840                 845             


Phe Val Ser Gln Pro Phe Thr Ile Val Pro Asp Asp Lys Lys Arg Pro 
    850                 855                 860                 


Ala Thr Ser Gly Thr Arg Tyr Ile Gly Val Asp Ile Gly Glu Tyr Gly 
865                 870                 875                 880 


Leu Ala Trp Ser Cys Trp Glu Phe Ala Pro Gly Tyr Trp Asn Gly Ser 
                885                 890                 895     


Val Val Asn Pro Ser Lys Val Thr Cys Leu Asp Tyr Gly Phe Leu Ala 
            900                 905                 910         


Glu Pro Gly Gln Arg Arg Ile Val Glu Arg Val Lys Lys Leu Arg Glu 
        915                 920                 925             


Ser Gln Ala Thr Lys Thr Phe Thr Ser Pro Asp Thr Tyr Ile Ala Arg 
    930                 935                 940                 


Leu Arg Glu Asn Val Val Ala Thr Tyr Gln Ala Gln Leu Glu Ala Leu 
945                 950                 955                 960 


Met Met Ala Tyr Asn Ala Gln Leu Val Phe Glu Ser Glu Ile Ser Ala 
                965                 970                 975     


Phe Glu Thr Gly Gly Asn Arg Val Lys Lys Ile Tyr Asp Ala Ile Lys 
            980                 985                 990         


Arg Ser Ser Val Phe Gly Arg Ser  Asp Ala Glu Ala Thr  Asp Asn Asn 
        995                 1000                 1005             


Gln His  Trp Gly Lys Asn Gly  Asn Arg Ser Ser Val  Lys Asp Pro 
    1010                 1015                 1020             


Asp Lys  Leu Arg Leu Asn Glu  Ala Gly Gln Val Ala  Ala Arg Val 
    1025                 1030                 1035             


Pro Trp  Ala Glu Pro Val Ser  Ala Trp Met Thr Ser  Gln Thr Cys 
    1040                 1045                 1050             


Ser Ala  Cys Gly Arg Val Tyr  Val Arg Ala Tyr Arg  Gly Lys Asn 
    1055                 1060                 1065             


Ser Asn  Glu Pro Asp Ser Gly  Ala Thr Gly Glu Val  Arg Tyr Phe 
    1070                 1075                 1080             


Asp Asn  Lys Gln Gln Lys Ile  Leu Thr Lys Thr Ile  Gly Ala Asp 
    1085                 1090                 1095             


Thr Val  Trp Val Thr Asp Gln  Glu Arg Lys Glu Phe  Glu Arg Gly 
    1100                 1105                 1110             


Val Tyr  Asn Ala Met Arg Pro  Asn Ala Phe Met Pro  Asp Gly Arg 
    1115                 1120                 1125             


Trp Thr  Ala Ala Gly Glu Ile  Leu Glu Ala Ala Leu  Lys Ser Arg 
    1130                 1135                 1140             


Gly Thr  Leu Asp Gly Gly Arg  Gly Phe Ala Gly Leu  His Leu Thr 
    1145                 1150                 1155             


Ser Lys  Ala Gln Val His Glu  Tyr Ile Glu Gly Thr  Gly Lys Ser 
    1160                 1165                 1170             


His Arg  Asp Ala His Gly Asn  Ser Ala Ile Phe Ile  Cys Pro Tyr 
    1175                 1180                 1185             


Thr Asp  Cys Gly His Ile Ala  Asp Ala Asp Leu Gln  Ala Ser Tyr 
    1190                 1195                 1200             


Asn Ile  Ala Leu Arg Gly Phe  Ala Tyr Ala Ile Val  Arg Lys Lys 
    1205                 1210                 1215             


His Pro  Glu Leu Phe Ala Gly  Ser Gly Ser Ser Thr  Asp Gly Asp 
    1220                 1225                 1230             


Glu Gly  Gly Gly Lys Lys Pro  Gln Gln Lys Gln Ala  Phe Ile Asp 
    1235                 1240                 1245             


Glu Ile  Val Arg Ala Ala Gly  Arg Ala Ser 
    1250                 1255             


<210>  51
<211>  3921
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanised nucleotide sequence WT AsCas12a

<400>  51
atgacacagt tcgagggctt taccaacctg tatcaggtga gcaagacact gcggtttgag       60

ctgatcccac agggcaagac cctgaagcac atccaggagc agggcttcat cgaggaggac      120

aaggcccgca atgatcacta caaggagctg aagcccatca tcgatcggat ctacaagacc      180

tatgccgacc agtgcctgca gctggtgcag ctggattggg agaacctgag cgccgccatc      240

gactcctata gaaaggagaa aaccgaggag acaaggaacg ccctgatcga ggagcaggcc      300

acatatcgca atgccatcca cgactacttc atcggccgga cagacaacct gaccgatgcc      360

atcaataaga gacacgccga gatctacaag ggcctgttca aggccgagct gtttaatggc      420

aaggtgctga agcagctggg caccgtgacc acaaccgagc acgagaacgc cctgctgcgg      480

agcttcgaca agtttacaac ctacttctcc ggcttttatg agaacaggaa gaacgtgttc      540

agcgccgagg atatcagcac agccatccca caccgcatcg tgcaggacaa cttccccaag      600

tttaaggaga attgtcacat cttcacacgc ctgatcaccg ccgtgcccag cctgcgggag      660

cactttgaga acgtgaagaa ggccatcggc atcttcgtga gcacctccat cgaggaggtg      720

ttttccttcc ctttttataa ccagctgctg acacagaccc agatcgacct gtataaccag      780

ctgctgggag gaatctctcg ggaggcaggc accgagaaga tcaagggcct gaacgaggtg      840

ctgaatctgg ccatccagaa gaatgatgag acagcccaca tcatcgcctc cctgccacac      900

agattcatcc ccctgtttaa gcagatcctg tccgatagga acaccctgtc tttcatcctg      960

gaggagttta agagcgacga ggaagtgatc cagtccttct gcaagtacaa gacactgctg     1020

agaaacgaga acgtgctgga gacagccgag gccctgttta acgagctgaa cagcatcgac     1080

ctgacacaca tcttcatcag ccacaagaag ctggagacaa tcagcagcgc cctgtgcgac     1140

cactgggata cactgaggaa tgccctgtat gagcggagaa tctccgagct gacaggcaag     1200

atcaccaagt ctgccaagga gaaggtgcag cgcagcctga agcacgagga tatcaacctg     1260

caggagatca tctctgccgc aggcaaggag ctgagcgagg ccttcaagca gaaaaccagc     1320

gagatcctgt cccacgcaca cgccgccctg gatcagccac tgcctacaac cctgaagaag     1380

caggaggaga aggagatcct gaagtctcag ctggacagcc tgctgggcct gtaccacctg     1440

ctggactggt ttgccgtgga tgagtccaac gaggtggacc ccgagttctc tgcccggctg     1500

accggcatca agctggagat ggagccttct ctgagcttct acaacaaggc cagaaattat     1560

gccaccaaga agccctactc cgtggagaag ttcaagctga actttcagat gcctacactg     1620

gcctctggct gggacgtgaa taaggagaag aacaatggcg ccatcctgtt tgtgaagaac     1680

ggcctgtact atctgggcat catgccaaag cagaagggca ggtataaggc cctgagcttc     1740

gagcccacag agaaaaccag cgagggcttt gataagatgt actatgacta cttccctgat     1800

gccgccaaga tgatcccaaa gtgcagcacc cagctgaagg ccgtgacagc ccactttcag     1860

acccacacaa cccccatcct gctgtccaac aatttcatcg agcctctgga gatcacaaag     1920

gagatctacg acctgaacaa tcctgagaag gagccaaaga agtttcagac agcctacgcc     1980

aagaaaaccg gcgaccagaa gggctacaga gaggccctgt gcaagtggat cgacttcaca     2040

agggattttc tgtccaagta taccaagaca acctctatcg atctgtctag cctgcggcca     2100

tcctctcagt ataaggacct gggcgagtac tatgccgagc tgaatcccct gctgtaccac     2160

atcagcttcc agagaatcgc cgagaaggag atcatggatg ccgtggagac aggcaagctg     2220

tacctgttcc agatctataa caaggacttt gccaagggcc accacggcaa gcctaatctg     2280

cacacactgt attggaccgg cctgttttct ccagagaacc tggccaagac aagcatcaag     2340

ctgaatggcc aggccgagct gttctaccgc cctaagtcca ggatgaagag gatggcacac     2400

cggctgggag agaagatgct gaacaagaag ctgaaggatc agaaaacccc aatccccgac     2460

accctgtacc aggagctgta cgactatgtg aatcacagac tgtcccacga cctgtctgat     2520

gaggccaggg ccctgctgcc caacgtgatc accaaggagg tgtctcacga gatcatcaag     2580

gataggcgct ttaccagcga caagttcttt ttccacgtgc ctatcacact gaactatcag     2640

gccgccaatt ccccatctaa gttcaaccag agggtgaatg cctacctgaa ggagcacccc     2700

gagacaccta tcatcggcat cgatcggggc gagagaaacc tgatctatat cacagtgatc     2760

gactccaccg gcaagatcct ggagcagcgg agcctgaaca ccatccagca gtttgattac     2820

cagaagaagc tggacaacag ggagaaggag agggtggcag caaggcaggc ctggtctgtg     2880

gtgggcacaa tcaaggatct gaagcagggc tatctgagcc aggtcatcca cgagatcgtg     2940

gacctgatga tccactacca ggccgtggtg gtgctggaga acctgaattt cggctttaag     3000

agcaagagga ccggcatcgc cgagaaggcc gtgtaccagc agttcgagaa gatgctgatc     3060

gataagctga attgcctggt gctgaaggac tatccagcag agaaagtggg aggcgtgctg     3120

aacccatacc agctgacaga ccagttcacc tcctttgcca agatgggcac ccagtctggc     3180

ttcctgtttt acgtgcctgc cccatataca tctaagatcg atcccctgac cggcttcgtg     3240

gaccccttcg tgtggaaaac catcaagaat cacgagagcc gcaagcactt cctggagggc     3300

ttcgactttc tgcactacga cgtgaaaacc ggcgacttca tcctgcactt taagatgaac     3360

agaaatctgt ccttccagag gggcctgccc ggctttatgc ctgcatggga tatcgtgttc     3420

gagaagaacg agacacagtt tgacgccaag ggcacccctt tcatcgccgg caagagaatc     3480

gtgccagtga tcgagaatca cagattcacc ggcagatacc gggacctgta tcctgccaac     3540

gagctgatcg ccctgctgga ggagaagggc atcgtgttca gggatggctc caacatcctg     3600

ccaaagctgc tggagaatga cgattctcac gccatcgaca ccatggtggc cctgatccgc     3660

agcgtgctgc agatgcggaa ctccaatgcc gccacaggcg aggactatat caacagcccc     3720

gtgcgcgatc tgaatggcgt gtgcttcgac tcccggtttc agaacccaga gtggcccatg     3780

gacgccgatg ccaatggcgc ctaccacatc gccctgaagg gccagctgct gctgaatcac     3840

ctgaaggaga gcaaggatct gaagctgcag aacggcatct ccaatcagga ctggctggcc     3900

tacatccagg agctgcgcaa c                                               3921


<210>  52
<211>  3387
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanised nucleotide sequence WT AaCas12b

<400>  52
atggccgtga agagcatgaa ggtgaagctg cgcctggaca acatgcccga gatccgcgcc       60

ggcctgtgga agctgcacac cgaggtgaac gccggcgtgc gctactacac cgagtggctg      120

agcctgctgc gccaggagaa cctgtaccgc cgcagcccca acggcgacgg cgagcaggag      180

tgctacaaga ccgccgagga gtgcaaggcc gagctgctgg agcgcctgcg cgcccgccag      240

gtggagaacg gccactgcgg ccccgccggc agcgacgacg agctgctgca gctggcccgc      300

cagctgtacg agctgctggt gccccaggcc atcggcgcca agggcgacgc ccagcagatc      360

gcccgcaagt tcctgagccc cctggccgac aaggacgccg tgggcggcct gggcatcgcc      420

aaggccggca acaagccccg ctgggtgcgc atgcgcgagg ccggcgagcc cggctgggag      480

gaggagaagg ccaaggccga ggcccgcaag agcaccgacc gcaccgccga cgtgctgcgc      540

gccctggccg acttcggcct gaagcccctg atgcgcgtgt acaccgacag cgacatgagc      600

agcgtgcagt ggaagcccct gcgcaagggc caggccgtgc gcacctggga ccgcgacatg      660

ttccagcagg ccatcgagcg catgatgagc tgggagagct ggaaccagcg cgtgggcgag      720

gcctacgcca agctggtgga gcagaagagc cgcttcgagc agaagaactt cgtgggccag      780

gagcacctgg tgcagctggt gaaccagctg cagcaggaca tgaaggaggc cagccacggc      840

ctggagagca aggagcagac cgcccactac ctgaccggcc gcgccctgcg cggcagcgac      900

aaggtgttcg agaagtggga gaagctggac cccgacgccc ccttcgacct gtacgacacc      960

gagatcaaga acgtgcagcg ccgcaacacc cgccgcttcg gcagccacga cctgttcgcc     1020

aagctggccg agcccaagta ccaggccctg tggcgcgagg acgccagctt cctgacccgc     1080

tacgccgtgt acaacagcat cgtgcgcaag ctgaaccacg ccaagatgtt cgccaccttc     1140

accctgcccg acgccaccgc ccaccccatc tggacccgct tcgacaagct gggcggcaac     1200

ctgcaccagt acaccttcct gttcaacgag ttcggcgagg gccgccacgc catccgcttc     1260

cagaagctgc tgaccgtgga ggacggcgtg gccaaggagg tggacgacgt gaccgtgccc     1320

atcagcatga gcgcccagct ggacgacctg ctgccccgcg acccccacga gctggtggcc     1380

ctgtacttcc aggactacgg cgccgagcag cacctggccg gcgagttcgg cggcgccaag     1440

atccagtacc gccgcgacca gctgaaccac ctgcacgccc gccgcggcgc ccgcgacgtg     1500

tacctgaacc tgagcgtgcg cgtgcagagc cagagcgagg cccgcggcga gcgccgcccc     1560

ccctacgccg ccgtgttccg cctggtgggc gacaaccacc gcgccttcgt gcacttcgac     1620

aagctgagcg actacctggc cgagcacccc gacgacggca agctgggcag cgagggcctg     1680

ctgagcggcc tgcgcgtgat gagcgtggac ctgggcctgc gcaccagcgc cagcatcagc     1740

gtgttccgcg tggcccgcaa ggacgagctg aagcccaaca gcgagggccg cgtgcccttc     1800

tgcttcccca tcgagggcaa cgagaacctg gtggccgtgc acgagcgcag ccagctgctg     1860

aagctgcccg gcgagaccga gagcaaggac ctgcgcgcca tccgcgagga gcgccagcgc     1920

accctgcgcc agctgcgcac ccagctggcc tacctgcgcc tgctggtgcg ctgcggcagc     1980

gaggacgtgg gccgccgcga gcgcagctgg gccaagctga tcgagcagcc catggacgcc     2040

aaccagatga cccccgactg gcgcgaggcc ttcgaggacg agctgcagaa gctgaagagc     2100

ctgtacggca tctgcggcga ccgcgagtgg accgaggccg tgtacgagag cgtgcgccgc     2160

gtgtggcgcc acatgggcaa gcaggtgcgc gactggcgca aggacgtgcg cagcggcgag     2220

cgccccaaga tccgcggcta ccagaaggac gtggtgggcg gcaacagcat cgagcagatc     2280

gagtacctgg agcgccagta caagttcctg aagagctgga gcttcttcgg caaggtgagc     2340

ggccaggtga tccgcgccga gaagggcagc cgcttcgcca tcaccctgcg cgagcacatc     2400

gaccacgcca aggaggaccg cctgaagaag ctggccgacc gcatcatcat ggaggccctg     2460

ggctacgtgt acgccctgga cgacgagcgc ggcaagggca agtgggtggc caagtacccc     2520

ccctgccagc tgatcctgct ggaggagctg agcgagtacc agttcaacaa cgaccgcccc     2580

cccagcgaga acaaccagct gatgcagtgg agccaccgcg gcgtgttcca ggagctgctg     2640

aaccaggccc aggtgcacga cctgctggtg ggcaccatgt acgccgcctt cagcagccgc     2700

ttcgacgccc gcaccggcgc ccccggcatc cgctgccgcc gcgtgcccgc ccgctgcgcc     2760

cgcgagcaga accccgagcc cttcccctgg tggctgaaca agttcgtggc cgagcacaag     2820

ctggacggct gccccctgcg cgccgacgac ctgatcccca ccggcgaggg cgagttcttc     2880

gtgagcccct tcagcgccga ggagggcgac ttccaccaga tccacgccga cctgaacgcc     2940

gcccagaacc tgcagcgccg cctgtggagc gacttcgaca tcagccagat ccgcctgcgc     3000

tgcgactggg gcgaggtgga cggcgagccc gtgctgatcc cccgcaccac cggcaagcgc     3060

accgccgaca gctacggcaa caaggtgttc tacaccaaga ccggcgtgac ctactacgag     3120

cgcgagcgcg gcaagaagcg ccgcaaggtg ttcgcccagg aggagctgag cgaggaggag     3180

gccgagctgc tggtggaggc cgacgaggcc cgcgagaaga gcgtggtgct gatgcgcgac     3240

cccagcggca tcatcaaccg cggcgactgg acccgccaga aggagttctg gagcatggtg     3300

aaccagcgca tcgagggcta cctggtgaag cagatccgca gccgcgtgcg cctgcaggag     3360

agcgcctgcg agaacaccgg cgacatc                                         3387


<210>  53
<211>  3774
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanised nucleotide sequence WT Cas12d15

<400>  53
atgaacgaaa agaagaccgc cacacagaga aggaacgcgc gcagaagaag aggagagaga       60

gccagaacca agagccagga gttgagaggc taccggctgc acgacgccag aatcgagttc      120

agcggcggac tcggcagcat gagaacagtg aaggtggaac tgctgaaccc cgacagctcc      180

agagaggatc cacagagagg ccagggcctg cagggtaaag tggccaaggc cgtgttcgac      240

gactacagag ccctgtacgg ccctatgaac atcgaggatt atctgagcga ccctgactgc      300

ccttcttttc tgggcctgtg ggttaaggcc gtttgtctgg gcgtgatcat gagcagaaag      360

accgccaccg acttcggcga attacgcgga ggctctaaga gcggacaggc gttcgatagc      420

attcccgagc acctgagaag acaactgatc aaactgaagt ggctggactg gtacgacaag      480

ggcatccgga agtcctccag caaggcctct cgtctgaagt ccctgaccga cgtgttcgcc      540

aatcctaagc agcctgacca gggagttatg gccgcgtggg agcagggcga gaagcttgct      600

gaaagctcca gagacattgc ggccctggga aggcgggaat ttaaggacaa gctgtttgct      660

atccctccac caacctcttc cgtggtgttg gatgacgacg tgaaggctac caaggtgagc      720

cgcgattggc agtgggccgt ggacccccag ttcaagctgc cgagcaccga cctggatatc      780

accagagccc tggaggaagt ggaccggcag tggttcgaac gcctgggcaa taacagaggc      840

atggtgcagc agttcttcgc tatcggcgat aacggcaacc acctgaacaa cggcctgttc      900

ggccacttct tcgcctcgat cagaagtgcc aacctggccg atatcgtggc cgaaatgggc      960

accgcctttg gttttagcgc tgaggaaaga gatatcgtgc ggcagcggct ggagaccctg     1020

cacgagtacg cccagggcct gcccgagaaa cctgtcctgg ctagcagatg ggccgagtac     1080

agaacagata tgacagccaa gctgggcagt tggtacagca acagaacctc caagggcgcc     1140

gcatctatca cacaggtgtg gggcacaatc aacaccgaga ccggagaggt gaaggatgat     1200

ggactagtca gaaccctgga aaacatccag agcgatttgc ctgacagctg tagcattaaa     1260

gaaggcatcc tgcaagagac cctggacttc atcggagata gacggagcag cacagacaga     1320

gctttcacag acgaactgga gctgtacctg gctaccctac ggagcgacct gaacacctgg     1380

tgccaggagc agagcgcctt gtgggaggaa aagcagcggc aggtcgctac gcctgcctct     1440

gatgagaaaa gcaaaaaggc cgacaatcca tgggccggca agggctccaa aacagataag     1500

tggctgggcg ccctgcatac ccggatccaa agcagccccc tgttctgggg cgtggacaag     1560

ctggagctgt ggaagaccct ggccaacctg aagcaagcca tcagagacga gatagacaag     1620

ctgaacgagc aggtggaggt gttcgggaga agcgcctatg acgaacccgt aggcaaagat     1680

gcggactcag gagagggaga tcggagagtg gaccagctga gctacctgag tgccagactg     1740

ggtgatcagg ctcatgaaga ggtcagacaa cggctggacg ccatcgccct ggccctcggc     1800

gtgaagttct ccgagcggga tgatcttcac cggtttttcg tgtctagcag agccagacgg     1860

cgggctgccc tgctggcgat gcccaatacc atcacagtgg gcaagctgcg ggagctggct     1920

gacctgacac cactgtggga acggatcaag aaaaagcctg aggagccaag actgctggcc     1980

gatacagtgg ccctcagcaa ggtggtgaac agcgcttgtg ccagccgggc taatcctagc     2040

gaccagatcg agcttacaac catccactct cggctcgacg gctactccaa gaacatcgga     2100

cacacagagt tcatcagcag agctacggtc cagagcacca acggagccca gaacaccgtc     2160

gccctggaca gcctggtgag ccccagactc ttctactaca acttccccaa tatcgtggaa     2220

agcgcagaac cccacgtgtc gcacctggaa gtggccacaa gaggcaatct ggggtctttc     2280

gaagaattcg ccgccaagga acaccggacc ttcgacagag aaaaccctca gaaagactcc     2340

agaaaccgga tcgatagcgt taaccctctg gccgtggcca gtagccggta ccagatccag     2400

ttcttcacct ggtgggccgg cctgcacagg agcaaggaga cagccctgga ggtcggcgga     2460

tcttttacca tcgccgaacg gcaagtgcgt ctggattggt cccaggagaa accccaggcc     2520

gtggtgtctg aagaactgag ggtgttcgtg tctcaacctt ttaccatcgt gcctgatgac     2580

aagaagcggc ctgctaccag cggcacccgg tacatcggcg tggacatcgg cgagtacggc     2640

ctcgcctgga gctgctggga attcgcccct ggctactgga atggttctgt tgtgaatccc     2700

agcaaggtga catgcctgga ctacggattc ctggccgaac caggccagag aagaatcgtg     2760

gagagagtga agaagctgag agagagccag gccaccaaga cattcaccag ccctgatacc     2820

tacatcgctc gtctgagaga gaatgtggtg gctacatacc aagcccagct ggaagcgctg     2880

atgatggcct acaacgccca actggtgttc gagtccgaga tctctgcctt tgaaacagga     2940

ggcaaccggg tcaagaaaat ctacgacgca attaaaaggt ctagcgtgtt tggccgcagc     3000

gacgctgagg ccaccgacaa taaccagcac tggggcaaga acggcaacag aagctccgtg     3060

aaggaccccg acaagctgag gctgaatgag gccggccagg tggccgccag agtgccttgg     3120

gccgagcctg tgtccgcatg gatgaccagc caaacatgca gcgcctgcgg ccgggtgtac     3180

gtgagagcct accgaggcaa gaactctaac gaacctgata gcggcgctac aggcgaagtg     3240

agatatttcg acaacaagca gcagaagatc ctgaccaaga ccatcggcgc cgacaccgtg     3300

tgggtgaccg atcaggagag aaaagagttc gagcggggcg tttataacgc catgcgcccc     3360

aacgccttca tgcctgacgg cagatggacc gccgctggcg agattctgga agccgccctc     3420

aaaagcagag gaaccctgga cggcggcaga ggcttcgctg gactgcacct gacatctaag     3480

gcccaggtgc acgagtacat cgagggcaca ggcaagagcc accgggacgc ccacggcaac     3540

tccgcaatct tcatctgccc ttacaccgac tgcggccata tcgccgacgc cgacctgcag     3600

gccagctaca acatcgccct gagaggcttc gcatacgcca tcgtacggaa gaagcaccct     3660

gagctgttcg caggatctgg cagctctact gacggcgacg aggggggagg caaaaagcct     3720

cagcagaagc aggcctttat cgacgagatt gtcagagccg ccggcagagc ctcc           3774


<210>  54
<211>  3921
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanised nucleotide sequence dCas12a

<400>  54
atgacacagt tcgagggctt taccaacctg tatcaggtga gcaagacact gcggtttgag       60

ctgatcccac agggcaagac cctgaagcac atccaggagc agggcttcat cgaggaggac      120

aaggcccgca atgatcacta caaggagctg aagcccatca tcgatcggat ctacaagacc      180

tatgccgacc agtgcctgca gctggtgcag ctggattggg agaacctgag cgccgccatc      240

gactcctata gaaaggagaa aaccgaggag acaaggaacg ccctgatcga ggagcaggcc      300

acatatcgca atgccatcca cgactacttc atcggccgga cagacaacct gaccgatgcc      360

atcaataaga gacacgccga gatctacaag ggcctgttca aggccgagct gtttaatggc      420

aaggtgctga agcagctggg caccgtgacc acaaccgagc acgagaacgc cctgctgcgg      480

agcttcgaca agtttacaac ctacttctcc ggcttttatg agaacaggaa gaacgtgttc      540

agcgccgagg atatcagcac agccatccca caccgcatcg tgcaggacaa cttccccaag      600

tttaaggaga attgtcacat cttcacacgc ctgatcaccg ccgtgcccag cctgcgggag      660

cactttgaga acgtgaagaa ggccatcggc atcttcgtga gcacctccat cgaggaggtg      720

ttttccttcc ctttttataa ccagctgctg acacagaccc agatcgacct gtataaccag      780

ctgctgggag gaatctctcg ggaggcaggc accgagaaga tcaagggcct gaacgaggtg      840

ctgaatctgg ccatccagaa gaatgatgag acagcccaca tcatcgcctc cctgccacac      900

agattcatcc ccctgtttaa gcagatcctg tccgatagga acaccctgtc tttcatcctg      960

gaggagttta agagcgacga ggaagtgatc cagtccttct gcaagtacaa gacactgctg     1020

agaaacgaga acgtgctgga gacagccgag gccctgttta acgagctgaa cagcatcgac     1080

ctgacacaca tcttcatcag ccacaagaag ctggagacaa tcagcagcgc cctgtgcgac     1140

cactgggata cactgaggaa tgccctgtat gagcggagaa tctccgagct gacaggcaag     1200

atcaccaagt ctgccaagga gaaggtgcag cgcagcctga agcacgagga tatcaacctg     1260

caggagatca tctctgccgc aggcaaggag ctgagcgagg ccttcaagca gaaaaccagc     1320

gagatcctgt cccacgcaca cgccgccctg gatcagccac tgcctacaac cctgaagaag     1380

caggaggaga aggagatcct gaagtctcag ctggacagcc tgctgggcct gtaccacctg     1440

ctggactggt ttgccgtgga tgagtccaac gaggtggacc ccgagttctc tgcccggctg     1500

accggcatca agctggagat ggagccttct ctgagcttct acaacaaggc cagaaattat     1560

gccaccaaga agccctactc cgtggagaag ttcaagctga actttcagat gcctacactg     1620

gcctctggct gggacgtgaa taaggagaag aacaatggcg ccatcctgtt tgtgaagaac     1680

ggcctgtact atctgggcat catgccaaag cagaagggca ggtataaggc cctgagcttc     1740

gagcccacag agaaaaccag cgagggcttt gataagatgt actatgacta cttccctgat     1800

gccgccaaga tgatcccaaa gtgcagcacc cagctgaagg ccgtgacagc ccactttcag     1860

acccacacaa cccccatcct gctgtccaac aatttcatcg agcctctgga gatcacaaag     1920

gagatctacg acctgaacaa tcctgagaag gagccaaaga agtttcagac agcctacgcc     1980

aagaaaaccg gcgaccagaa gggctacaga gaggccctgt gcaagtggat cgacttcaca     2040

agggattttc tgtccaagta taccaagaca acctctatcg atctgtctag cctgcggcca     2100

tcctctcagt ataaggacct gggcgagtac tatgccgagc tgaatcccct gctgtaccac     2160

atcagcttcc agagaatcgc cgagaaggag atcatggatg ccgtggagac aggcaagctg     2220

tacctgttcc agatctataa caaggacttt gccaagggcc accacggcaa gcctaatctg     2280

cacacactgt attggaccgg cctgttttct ccagagaacc tggccaagac aagcatcaag     2340

ctgaatggcc aggccgagct gttctaccgc cctaagtcca ggatgaagag gatggcacac     2400

cggctgggag agaagatgct gaacaagaag ctgaaggatc agaaaacccc aatccccgac     2460

accctgtacc aggagctgta cgactatgtg aatcacagac tgtcccacga cctgtctgat     2520

gaggccaggg ccctgctgcc caacgtgatc accaaggagg tgtctcacga gatcatcaag     2580

gataggcgct ttaccagcga caagttcttt ttccacgtgc ctatcacact gaactatcag     2640

gccgccaatt ccccatctaa gttcaaccag agggtgaatg cctacctgaa ggagcacccc     2700

gagacaccta tcatcggcat cgcccggggc gagagaaacc tgatctatat cacagtgatc     2760

gactccaccg gcaagatcct ggagcagcgg agcctgaaca ccatccagca gtttgattac     2820

cagaagaagc tggacaacag ggagaaggag agggtggcag caaggcaggc ctggtctgtg     2880

gtgggcacaa tcaaggatct gaagcagggc tatctgagcc aggtcatcca cgagatcgtg     2940

gacctgatga tccactacca ggccgtggtg gtgctggaga acctgaattt cggctttaag     3000

agcaagagga ccggcatcgc cgagaaggcc gtgtaccagc agttcgagaa gatgctgatc     3060

gataagctga attgcctggt gctgaaggac tatccagcag agaaagtggg aggcgtgctg     3120

aacccatacc agctgacaga ccagttcacc tcctttgcca agatgggcac ccagtctggc     3180

ttcctgtttt acgtgcctgc cccatataca tctaagatcg atcccctgac cggcttcgtg     3240

gaccccttcg tgtggaaaac catcaagaat cacgagagcc gcaagcactt cctggagggc     3300

ttcgactttc tgcactacga cgtgaaaacc ggcgacttca tcctgcactt taagatgaac     3360

agaaatctgt ccttccagag gggcctgccc ggctttatgc ctgcatggga tatcgtgttc     3420

gagaagaacg agacacagtt tgacgccaag ggcacccctt tcatcgccgg caagagaatc     3480

gtgccagtga tcgagaatca cagattcacc ggcagatacc gggacctgta tcctgccaac     3540

gagctgatcg ccctgctgga ggagaagggc atcgtgttca gggatggctc caacatcctg     3600

ccaaagctgc tggagaatga cgattctcac gccatcgaca ccatggtggc cctgatccgc     3660

agcgtgctgc agatgcggaa ctccaatgcc gccacaggcg aggactatat caacagcccc     3720

gtgcgcgatc tgaatggcgt gtgcttcgac tcccggtttc agaacccaga gtggcccatg     3780

gacgccgatg ccaatggcgc ctaccacatc gccctgaagg gccagctgct gctgaatcac     3840

ctgaaggaga gcaaggatct gaagctgcag aacggcatct ccaatcagga ctggctggcc     3900

tacatccagg agctgcgcaa c                                               3921


<210>  55
<211>  3387
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanised nucleotide sequence dCas12b

<400>  55
atggccgtga agagcatgaa ggtgaagctg cgcctggaca acatgcccga gatccgcgcc       60

ggcctgtgga agctgcacac cgaggtgaac gccggcgtgc gctactacac cgagtggctg      120

agcctgctgc gccaggagaa cctgtaccgc cgcagcccca acggcgacgg cgagcaggag      180

tgctacaaga ccgccgagga gtgcaaggcc gagctgctgg agcgcctgcg cgcccgccag      240

gtggagaacg gccactgcgg ccccgccggc agcgacgacg agctgctgca gctggcccgc      300

cagctgtacg agctgctggt gccccaggcc atcggcgcca agggcgacgc ccagcagatc      360

gcccgcaagt tcctgagccc cctggccgac aaggacgccg tgggcggcct gggcatcgcc      420

aaggccggca acaagccccg ctgggtgcgc atgcgcgagg ccggcgagcc cggctgggag      480

gaggagaagg ccaaggccga ggcccgcaag agcaccgacc gcaccgccga cgtgctgcgc      540

gccctggccg acttcggcct gaagcccctg atgcgcgtgt acaccgacag cgacatgagc      600

agcgtgcagt ggaagcccct gcgcaagggc caggccgtgc gcacctggga ccgcgacatg      660

ttccagcagg ccatcgagcg catgatgagc tgggagagct ggaaccagcg cgtgggcgag      720

gcctacgcca agctggtgga gcagaagagc cgcttcgagc agaagaactt cgtgggccag      780

gagcacctgg tgcagctggt gaaccagctg cagcaggaca tgaaggaggc cagccacggc      840

ctggagagca aggagcagac cgcccactac ctgaccggcc gcgccctgcg cggcagcgac      900

aaggtgttcg agaagtggga gaagctggac cccgacgccc ccttcgacct gtacgacacc      960

gagatcaaga acgtgcagcg ccgcaacacc cgccgcttcg gcagccacga cctgttcgcc     1020

aagctggccg agcccaagta ccaggccctg tggcgcgagg acgccagctt cctgacccgc     1080

tacgccgtgt acaacagcat cgtgcgcaag ctgaaccacg ccaagatgtt cgccaccttc     1140

accctgcccg acgccaccgc ccaccccatc tggacccgct tcgacaagct gggcggcaac     1200

ctgcaccagt acaccttcct gttcaacgag ttcggcgagg gccgccacgc catccgcttc     1260

cagaagctgc tgaccgtgga ggacggcgtg gccaaggagg tggacgacgt gaccgtgccc     1320

atcagcatga gcgcccagct ggacgacctg ctgccccgcg acccccacga gctggtggcc     1380

ctgtacttcc aggactacgg cgccgagcag cacctggccg gcgagttcgg cggcgccaag     1440

atccagtacc gccgcgacca gctgaaccac ctgcacgccc gccgcggcgc ccgcgacgtg     1500

tacctgaacc tgagcgtgcg cgtgcagagc cagagcgagg cccgcggcga gcgccgcccc     1560

ccctacgccg ccgtgttccg cctggtgggc gacaaccacc gcgccttcgt gcacttcgac     1620

aagctgagcg actacctggc cgagcacccc gacgacggca agctgggcag cgagggcctg     1680

ctgagcggcc tgcgcgtgat gagcgtggcc ctgggcctgc gcaccagcgc cagcatcagc     1740

gtgttccgcg tggcccgcaa ggacgagctg aagcccaaca gcgagggccg cgtgcccttc     1800

tgcttcccca tcgagggcaa cgagaacctg gtggccgtgc acgagcgcag ccagctgctg     1860

aagctgcccg gcgagaccga gagcaaggac ctgcgcgcca tccgcgagga gcgccagcgc     1920

accctgcgcc agctgcgcac ccagctggcc tacctgcgcc tgctggtgcg ctgcggcagc     1980

gaggacgtgg gccgccgcga gcgcagctgg gccaagctga tcgagcagcc catggacgcc     2040

aaccagatga cccccgactg gcgcgaggcc ttcgaggacg agctgcagaa gctgaagagc     2100

ctgtacggca tctgcggcga ccgcgagtgg accgaggccg tgtacgagag cgtgcgccgc     2160

gtgtggcgcc acatgggcaa gcaggtgcgc gactggcgca aggacgtgcg cagcggcgag     2220

cgccccaaga tccgcggcta ccagaaggac gtggtgggcg gcaacagcat cgagcagatc     2280

gagtacctgg agcgccagta caagttcctg aagagctgga gcttcttcgg caaggtgagc     2340

ggccaggtga tccgcgccga gaagggcagc cgcttcgcca tcaccctgcg cgagcacatc     2400

gaccacgcca aggaggaccg cctgaagaag ctggccgacc gcatcatcat ggaggccctg     2460

ggctacgtgt acgccctgga cgacgagcgc ggcaagggca agtgggtggc caagtacccc     2520

ccctgccagc tgatcctgct ggaggagctg agcgagtacc agttcaacaa cgaccgcccc     2580

cccagcgaga acaaccagct gatgcagtgg agccaccgcg gcgtgttcca ggagctgctg     2640

aaccaggccc aggtgcacga cctgctggtg ggcaccatgt acgccgcctt cagcagccgc     2700

ttcgacgccc gcaccggcgc ccccggcatc cgctgccgcc gcgtgcccgc ccgctgcgcc     2760

cgcgagcaga accccgagcc cttcccctgg tggctgaaca agttcgtggc cgagcacaag     2820

ctggacggct gccccctgcg cgccgacgac ctgatcccca ccggcgaggg cgagttcttc     2880

gtgagcccct tcagcgccga ggagggcgac ttccaccaga tccacgccga cctgaacgcc     2940

gcccagaacc tgcagcgccg cctgtggagc gacttcgaca tcagccagat ccgcctgcgc     3000

tgcgactggg gcgaggtgga cggcgagccc gtgctgatcc cccgcaccac cggcaagcgc     3060

accgccgaca gctacggcaa caaggtgttc tacaccaaga ccggcgtgac ctactacgag     3120

cgcgagcgcg gcaagaagcg ccgcaaggtg ttcgcccagg aggagctgag cgaggaggag     3180

gccgagctgc tggtggaggc cgacgaggcc cgcgagaaga gcgtggtgct gatgcgcgac     3240

cccagcggca tcatcaaccg cggcgactgg acccgccaga aggagttctg gagcatggtg     3300

aaccagcgca tcgagggcta cctggtgaag cagatccgca gccgcgtgcg cctgcaggag     3360

agcgcctgcg agaacaccgg cgacatc                                         3387


<210>  56
<211>  3774
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanised nucleotide sequence dCas12d

<400>  56
atgaacgaaa agaagaccgc cacacagaga aggaacgcgc gcagaagaag aggagagaga       60

gccagaacca agagccagga gttgagaggc taccggctgc acgacgccag aatcgagttc      120

agcggcggac tcggcagcat gagaacagtg aaggtggaac tgctgaaccc cgacagctcc      180

agagaggatc cacagagagg ccagggcctg cagggtaaag tggccaaggc cgtgttcgac      240

gactacagag ccctgtacgg ccctatgaac atcgaggatt atctgagcga ccctgactgc      300

ccttcttttc tgggcctgtg ggttaaggcc gtttgtctgg gcgtgatcat gagcagaaag      360

accgccaccg acttcggcga attacgcgga ggctctaaga gcggacaggc gttcgatagc      420

attcccgagc acctgagaag acaactgatc aaactgaagt ggctggactg gtacgacaag      480

ggcatccgga agtcctccag caaggcctct cgtctgaagt ccctgaccga cgtgttcgcc      540

aatcctaagc agcctgacca gggagttatg gccgcgtggg agcagggcga gaagcttgct      600

gaaagctcca gagacattgc ggccctggga aggcgggaat ttaaggacaa gctgtttgct      660

atccctccac caacctcttc cgtggtgttg gatgacgacg tgaaggctac caaggtgagc      720

cgcgattggc agtgggccgt ggacccccag ttcaagctgc cgagcaccga cctggatatc      780

accagagccc tggaggaagt ggaccggcag tggttcgaac gcctgggcaa taacagaggc      840

atggtgcagc agttcttcgc tatcggcgat aacggcaacc acctgaacaa cggcctgttc      900

ggccacttct tcgcctcgat cagaagtgcc aacctggccg atatcgtggc cgaaatgggc      960

accgcctttg gttttagcgc tgaggaaaga gatatcgtgc ggcagcggct ggagaccctg     1020

cacgagtacg cccagggcct gcccgagaaa cctgtcctgg ctagcagatg ggccgagtac     1080

agaacagata tgacagccaa gctgggcagt tggtacagca acagaacctc caagggcgcc     1140

gcatctatca cacaggtgtg gggcacaatc aacaccgaga ccggagaggt gaaggatgat     1200

ggactagtca gaaccctgga aaacatccag agcgatttgc ctgacagctg tagcattaaa     1260

gaaggcatcc tgcaagagac cctggacttc atcggagata gacggagcag cacagacaga     1320

gctttcacag acgaactgga gctgtacctg gctaccctac ggagcgacct gaacacctgg     1380

tgccaggagc agagcgcctt gtgggaggaa aagcagcggc aggtcgctac gcctgcctct     1440

gatgagaaaa gcaaaaaggc cgacaatcca tgggccggca agggctccaa aacagataag     1500

tggctgggcg ccctgcatac ccggatccaa agcagccccc tgttctgggg cgtggacaag     1560

ctggagctgt ggaagaccct ggccaacctg aagcaagcca tcagagacga gatagacaag     1620

ctgaacgagc aggtggaggt gttcgggaga agcgcctatg acgaacccgt aggcaaagat     1680

gcggactcag gagagggaga tcggagagtg gaccagctga gctacctgag tgccagactg     1740

ggtgatcagg ctcatgaaga ggtcagacaa cggctggacg ccatcgccct ggccctcggc     1800

gtgaagttct ccgagcggga tgatcttcac cggtttttcg tgtctagcag agccagacgg     1860

cgggctgccc tgctggcgat gcccaatacc atcacagtgg gcaagctgcg ggagctggct     1920

gacctgacac cactgtggga acggatcaag aaaaagcctg aggagccaag actgctggcc     1980

gatacagtgg ccctcagcaa ggtggtgaac agcgcttgtg ccagccgggc taatcctagc     2040

gaccagatcg agcttacaac catccactct cggctcgacg gctactccaa gaacatcgga     2100

cacacagagt tcatcagcag agctacggtc cagagcacca acggagccca gaacaccgtc     2160

gccctggaca gcctggtgag ccccagactc ttctactaca acttccccaa tatcgtggaa     2220

agcgcagaac cccacgtgtc gcacctggaa gtggccacaa gaggcaatct ggggtctttc     2280

gaagaattcg ccgccaagga acaccggacc ttcgacagag aaaaccctca gaaagactcc     2340

agaaaccgga tcgatagcgt taaccctctg gccgtggcca gtagccggta ccagatccag     2400

ttcttcacct ggtgggccgg cctgcacagg agcaaggaga cagccctgga ggtcggcgga     2460

tcttttacca tcgccgaacg gcaagtgcgt ctggattggt cccaggagaa accccaggcc     2520

gtggtgtctg aagaactgag ggtgttcgtg tctcaacctt ttaccatcgt gcctgatgac     2580

aagaagcggc ctgctaccag cggcacccgg tacatcggcg tggccatcgg cgagtacggc     2640

ctcgcctgga gctgctggga attcgcccct ggctactgga atggttctgt tgtgaatccc     2700

agcaaggtga catgcctgga ctacggattc ctggccgaac caggccagag aagaatcgtg     2760

gagagagtga agaagctgag agagagccag gccaccaaga cattcaccag ccctgatacc     2820

tacatcgctc gtctgagaga gaatgtggtg gctacatacc aagcccagct ggaagcgctg     2880

atgatggcct acaacgccca actggtgttc gcctccgaga tctctgcctt tgaaacagga     2940

ggcaaccggg tcaagaaaat ctacgacgca attaaaaggt ctagcgtgtt tggccgcagc     3000

gacgctgagg ccaccgacaa taaccagcac tggggcaaga acggcaacag aagctccgtg     3060

aaggaccccg acaagctgag gctgaatgag gccggccagg tggccgccag agtgccttgg     3120

gccgagcctg tgtccgcatg gatgaccagc caaacatgca gcgcctgcgg ccgggtgtac     3180

gtgagagcct accgaggcaa gaactctaac gaacctgata gcggcgctac aggcgaagtg     3240

agatatttcg acaacaagca gcagaagatc ctgaccaaga ccatcggcgc cgacaccgtg     3300

tgggtgaccg atcaggagag aaaagagttc gagcggggcg tttataacgc catgcgcccc     3360

aacgccttca tgcctgacgg cagatggacc gccgctggcg agattctgga agccgccctc     3420

aaaagcagag gaaccctgga cggcggcaga ggcttcgctg gactgcacct gacatctaag     3480

gcccaggtgc acgagtacat cgagggcaca ggcaagagcc accgggacgc ccacggcaac     3540

tccgcaatct tcatctgccc ttacaccgac tgcggccata tcgccgacgc cgccctgcag     3600

gccagctaca acatcgccct gagaggcttc gcatacgcca tcgtacggaa gaagcaccct     3660

gagctgttcg caggatctgg cagctctact gacggcgacg aggggggagg caaaaagcct     3720

cagcagaagc aggcctttat cgacgagatt gtcagagccg ccggcagagc ctcc           3774


<210>  57
<211>  1307
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence dAsCas12a

<400>  57

Met Thr Gln Phe Glu Gly Phe Thr Asn Leu Tyr Gln Val Ser Lys Thr 
1               5                   10                  15      


Leu Arg Phe Glu Leu Ile Pro Gln Gly Lys Thr Leu Lys His Ile Gln 
            20                  25                  30          


Glu Gln Gly Phe Ile Glu Glu Asp Lys Ala Arg Asn Asp His Tyr Lys 
        35                  40                  45              


Glu Leu Lys Pro Ile Ile Asp Arg Ile Tyr Lys Thr Tyr Ala Asp Gln 
    50                  55                  60                  


Cys Leu Gln Leu Val Gln Leu Asp Trp Glu Asn Leu Ser Ala Ala Ile 
65                  70                  75                  80  


Asp Ser Tyr Arg Lys Glu Lys Thr Glu Glu Thr Arg Asn Ala Leu Ile 
                85                  90                  95      


Glu Glu Gln Ala Thr Tyr Arg Asn Ala Ile His Asp Tyr Phe Ile Gly 
            100                 105                 110         


Arg Thr Asp Asn Leu Thr Asp Ala Ile Asn Lys Arg His Ala Glu Ile 
        115                 120                 125             


Tyr Lys Gly Leu Phe Lys Ala Glu Leu Phe Asn Gly Lys Val Leu Lys 
    130                 135                 140                 


Gln Leu Gly Thr Val Thr Thr Thr Glu His Glu Asn Ala Leu Leu Arg 
145                 150                 155                 160 


Ser Phe Asp Lys Phe Thr Thr Tyr Phe Ser Gly Phe Tyr Glu Asn Arg 
                165                 170                 175     


Lys Asn Val Phe Ser Ala Glu Asp Ile Ser Thr Ala Ile Pro His Arg 
            180                 185                 190         


Ile Val Gln Asp Asn Phe Pro Lys Phe Lys Glu Asn Cys His Ile Phe 
        195                 200                 205             


Thr Arg Leu Ile Thr Ala Val Pro Ser Leu Arg Glu His Phe Glu Asn 
    210                 215                 220                 


Val Lys Lys Ala Ile Gly Ile Phe Val Ser Thr Ser Ile Glu Glu Val 
225                 230                 235                 240 


Phe Ser Phe Pro Phe Tyr Asn Gln Leu Leu Thr Gln Thr Gln Ile Asp 
                245                 250                 255     


Leu Tyr Asn Gln Leu Leu Gly Gly Ile Ser Arg Glu Ala Gly Thr Glu 
            260                 265                 270         


Lys Ile Lys Gly Leu Asn Glu Val Leu Asn Leu Ala Ile Gln Lys Asn 
        275                 280                 285             


Asp Glu Thr Ala His Ile Ile Ala Ser Leu Pro His Arg Phe Ile Pro 
    290                 295                 300                 


Leu Phe Lys Gln Ile Leu Ser Asp Arg Asn Thr Leu Ser Phe Ile Leu 
305                 310                 315                 320 


Glu Glu Phe Lys Ser Asp Glu Glu Val Ile Gln Ser Phe Cys Lys Tyr 
                325                 330                 335     


Lys Thr Leu Leu Arg Asn Glu Asn Val Leu Glu Thr Ala Glu Ala Leu 
            340                 345                 350         


Phe Asn Glu Leu Asn Ser Ile Asp Leu Thr His Ile Phe Ile Ser His 
        355                 360                 365             


Lys Lys Leu Glu Thr Ile Ser Ser Ala Leu Cys Asp His Trp Asp Thr 
    370                 375                 380                 


Leu Arg Asn Ala Leu Tyr Glu Arg Arg Ile Ser Glu Leu Thr Gly Lys 
385                 390                 395                 400 


Ile Thr Lys Ser Ala Lys Glu Lys Val Gln Arg Ser Leu Lys His Glu 
                405                 410                 415     


Asp Ile Asn Leu Gln Glu Ile Ile Ser Ala Ala Gly Lys Glu Leu Ser 
            420                 425                 430         


Glu Ala Phe Lys Gln Lys Thr Ser Glu Ile Leu Ser His Ala His Ala 
        435                 440                 445             


Ala Leu Asp Gln Pro Leu Pro Thr Thr Leu Lys Lys Gln Glu Glu Lys 
    450                 455                 460                 


Glu Ile Leu Lys Ser Gln Leu Asp Ser Leu Leu Gly Leu Tyr His Leu 
465                 470                 475                 480 


Leu Asp Trp Phe Ala Val Asp Glu Ser Asn Glu Val Asp Pro Glu Phe 
                485                 490                 495     


Ser Ala Arg Leu Thr Gly Ile Lys Leu Glu Met Glu Pro Ser Leu Ser 
            500                 505                 510         


Phe Tyr Asn Lys Ala Arg Asn Tyr Ala Thr Lys Lys Pro Tyr Ser Val 
        515                 520                 525             


Glu Lys Phe Lys Leu Asn Phe Gln Met Pro Thr Leu Ala Ser Gly Trp 
    530                 535                 540                 


Asp Val Asn Lys Glu Lys Asn Asn Gly Ala Ile Leu Phe Val Lys Asn 
545                 550                 555                 560 


Gly Leu Tyr Tyr Leu Gly Ile Met Pro Lys Gln Lys Gly Arg Tyr Lys 
                565                 570                 575     


Ala Leu Ser Phe Glu Pro Thr Glu Lys Thr Ser Glu Gly Phe Asp Lys 
            580                 585                 590         


Met Tyr Tyr Asp Tyr Phe Pro Asp Ala Ala Lys Met Ile Pro Lys Cys 
        595                 600                 605             


Ser Thr Gln Leu Lys Ala Val Thr Ala His Phe Gln Thr His Thr Thr 
    610                 615                 620                 


Pro Ile Leu Leu Ser Asn Asn Phe Ile Glu Pro Leu Glu Ile Thr Lys 
625                 630                 635                 640 


Glu Ile Tyr Asp Leu Asn Asn Pro Glu Lys Glu Pro Lys Lys Phe Gln 
                645                 650                 655     


Thr Ala Tyr Ala Lys Lys Thr Gly Asp Gln Lys Gly Tyr Arg Glu Ala 
            660                 665                 670         


Leu Cys Lys Trp Ile Asp Phe Thr Arg Asp Phe Leu Ser Lys Tyr Thr 
        675                 680                 685             


Lys Thr Thr Ser Ile Asp Leu Ser Ser Leu Arg Pro Ser Ser Gln Tyr 
    690                 695                 700                 


Lys Asp Leu Gly Glu Tyr Tyr Ala Glu Leu Asn Pro Leu Leu Tyr His 
705                 710                 715                 720 


Ile Ser Phe Gln Arg Ile Ala Glu Lys Glu Ile Met Asp Ala Val Glu 
                725                 730                 735     


Thr Gly Lys Leu Tyr Leu Phe Gln Ile Tyr Asn Lys Asp Phe Ala Lys 
            740                 745                 750         


Gly His His Gly Lys Pro Asn Leu His Thr Leu Tyr Trp Thr Gly Leu 
        755                 760                 765             


Phe Ser Pro Glu Asn Leu Ala Lys Thr Ser Ile Lys Leu Asn Gly Gln 
    770                 775                 780                 


Ala Glu Leu Phe Tyr Arg Pro Lys Ser Arg Met Lys Arg Met Ala His 
785                 790                 795                 800 


Arg Leu Gly Glu Lys Met Leu Asn Lys Lys Leu Lys Asp Gln Lys Thr 
                805                 810                 815     


Pro Ile Pro Asp Thr Leu Tyr Gln Glu Leu Tyr Asp Tyr Val Asn His 
            820                 825                 830         


Arg Leu Ser His Asp Leu Ser Asp Glu Ala Arg Ala Leu Leu Pro Asn 
        835                 840                 845             


Val Ile Thr Lys Glu Val Ser His Glu Ile Ile Lys Asp Arg Arg Phe 
    850                 855                 860                 


Thr Ser Asp Lys Phe Phe Phe His Val Pro Ile Thr Leu Asn Tyr Gln 
865                 870                 875                 880 


Ala Ala Asn Ser Pro Ser Lys Phe Asn Gln Arg Val Asn Ala Tyr Leu 
                885                 890                 895     


Lys Glu His Pro Glu Thr Pro Ile Ile Gly Ile Ala Arg Gly Glu Arg 
            900                 905                 910         


Asn Leu Ile Tyr Ile Thr Val Ile Asp Ser Thr Gly Lys Ile Leu Glu 
        915                 920                 925             


Gln Arg Ser Leu Asn Thr Ile Gln Gln Phe Asp Tyr Gln Lys Lys Leu 
    930                 935                 940                 


Asp Asn Arg Glu Lys Glu Arg Val Ala Ala Arg Gln Ala Trp Ser Val 
945                 950                 955                 960 


Val Gly Thr Ile Lys Asp Leu Lys Gln Gly Tyr Leu Ser Gln Val Ile 
                965                 970                 975     


His Glu Ile Val Asp Leu Met Ile His Tyr Gln Ala Val Val Val Leu 
            980                 985                 990         


Glu Asn Leu Asn Phe Gly Phe Lys  Ser Lys Arg Thr Gly  Ile Ala Glu 
        995                 1000                 1005             


Lys Ala  Val Tyr Gln Gln Phe  Glu Lys Met Leu Ile  Asp Lys Leu 
    1010                 1015                 1020             


Asn Cys  Leu Val Leu Lys Asp  Tyr Pro Ala Glu Lys  Val Gly Gly 
    1025                 1030                 1035             


Val Leu  Asn Pro Tyr Gln Leu  Thr Asp Gln Phe Thr  Ser Phe Ala 
    1040                 1045                 1050             


Lys Met  Gly Thr Gln Ser Gly  Phe Leu Phe Tyr Val  Pro Ala Pro 
    1055                 1060                 1065             


Tyr Thr  Ser Lys Ile Asp Pro  Leu Thr Gly Phe Val  Asp Pro Phe 
    1070                 1075                 1080             


Val Trp  Lys Thr Ile Lys Asn  His Glu Ser Arg Lys  His Phe Leu 
    1085                 1090                 1095             


Glu Gly  Phe Asp Phe Leu His  Tyr Asp Val Lys Thr  Gly Asp Phe 
    1100                 1105                 1110             


Ile Leu  His Phe Lys Met Asn  Arg Asn Leu Ser Phe  Gln Arg Gly 
    1115                 1120                 1125             


Leu Pro  Gly Phe Met Pro Ala  Trp Asp Ile Val Phe  Glu Lys Asn 
    1130                 1135                 1140             


Glu Thr  Gln Phe Asp Ala Lys  Gly Thr Pro Phe Ile  Ala Gly Lys 
    1145                 1150                 1155             


Arg Ile  Val Pro Val Ile Glu  Asn His Arg Phe Thr  Gly Arg Tyr 
    1160                 1165                 1170             


Arg Asp  Leu Tyr Pro Ala Asn  Glu Leu Ile Ala Leu  Leu Glu Glu 
    1175                 1180                 1185             


Lys Gly  Ile Val Phe Arg Asp  Gly Ser Asn Ile Leu  Pro Lys Leu 
    1190                 1195                 1200             


Leu Glu  Asn Asp Asp Ser His  Ala Ile Asp Thr Met  Val Ala Leu 
    1205                 1210                 1215             


Ile Arg  Ser Val Leu Gln Met  Arg Asn Ser Asn Ala  Ala Thr Gly 
    1220                 1225                 1230             


Glu Asp  Tyr Ile Asn Ser Pro  Val Arg Asp Leu Asn  Gly Val Cys 
    1235                 1240                 1245             


Phe Asp  Ser Arg Phe Gln Asn  Pro Glu Trp Pro Met  Asp Ala Asp 
    1250                 1255                 1260             


Ala Asn  Gly Ala Tyr His Ile  Ala Leu Lys Gly Gln  Leu Leu Leu 
    1265                 1270                 1275             


Asn His  Leu Lys Glu Ser Lys  Asp Leu Lys Leu Gln  Asn Gly Ile 
    1280                 1285                 1290             


Ser Asn  Gln Asp Trp Leu Ala  Tyr Ile Gln Glu Leu  Arg Asn 
    1295                 1300                 1305         


<210>  58
<211>  1129
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence dAaCas12b

<400>  58

Met Ala Val Lys Ser Met Lys Val Lys Leu Arg Leu Asp Asn Met Pro 
1               5                   10                  15      


Glu Ile Arg Ala Gly Leu Trp Lys Leu His Thr Glu Val Asn Ala Gly 
            20                  25                  30          


Val Arg Tyr Tyr Thr Glu Trp Leu Ser Leu Leu Arg Gln Glu Asn Leu 
        35                  40                  45              


Tyr Arg Arg Ser Pro Asn Gly Asp Gly Glu Gln Glu Cys Tyr Lys Thr 
    50                  55                  60                  


Ala Glu Glu Cys Lys Ala Glu Leu Leu Glu Arg Leu Arg Ala Arg Gln 
65                  70                  75                  80  


Val Glu Asn Gly His Cys Gly Pro Ala Gly Ser Asp Asp Glu Leu Leu 
                85                  90                  95      


Gln Leu Ala Arg Gln Leu Tyr Glu Leu Leu Val Pro Gln Ala Ile Gly 
            100                 105                 110         


Ala Lys Gly Asp Ala Gln Gln Ile Ala Arg Lys Phe Leu Ser Pro Leu 
        115                 120                 125             


Ala Asp Lys Asp Ala Val Gly Gly Leu Gly Ile Ala Lys Ala Gly Asn 
    130                 135                 140                 


Lys Pro Arg Trp Val Arg Met Arg Glu Ala Gly Glu Pro Gly Trp Glu 
145                 150                 155                 160 


Glu Glu Lys Ala Lys Ala Glu Ala Arg Lys Ser Thr Asp Arg Thr Ala 
                165                 170                 175     


Asp Val Leu Arg Ala Leu Ala Asp Phe Gly Leu Lys Pro Leu Met Arg 
            180                 185                 190         


Val Tyr Thr Asp Ser Asp Met Ser Ser Val Gln Trp Lys Pro Leu Arg 
        195                 200                 205             


Lys Gly Gln Ala Val Arg Thr Trp Asp Arg Asp Met Phe Gln Gln Ala 
    210                 215                 220                 


Ile Glu Arg Met Met Ser Trp Glu Ser Trp Asn Gln Arg Val Gly Glu 
225                 230                 235                 240 


Ala Tyr Ala Lys Leu Val Glu Gln Lys Ser Arg Phe Glu Gln Lys Asn 
                245                 250                 255     


Phe Val Gly Gln Glu His Leu Val Gln Leu Val Asn Gln Leu Gln Gln 
            260                 265                 270         


Asp Met Lys Glu Ala Ser His Gly Leu Glu Ser Lys Glu Gln Thr Ala 
        275                 280                 285             


His Tyr Leu Thr Gly Arg Ala Leu Arg Gly Ser Asp Lys Val Phe Glu 
    290                 295                 300                 


Lys Trp Glu Lys Leu Asp Pro Asp Ala Pro Phe Asp Leu Tyr Asp Thr 
305                 310                 315                 320 


Glu Ile Lys Asn Val Gln Arg Arg Asn Thr Arg Arg Phe Gly Ser His 
                325                 330                 335     


Asp Leu Phe Ala Lys Leu Ala Glu Pro Lys Tyr Gln Ala Leu Trp Arg 
            340                 345                 350         


Glu Asp Ala Ser Phe Leu Thr Arg Tyr Ala Val Tyr Asn Ser Ile Val 
        355                 360                 365             


Arg Lys Leu Asn His Ala Lys Met Phe Ala Thr Phe Thr Leu Pro Asp 
    370                 375                 380                 


Ala Thr Ala His Pro Ile Trp Thr Arg Phe Asp Lys Leu Gly Gly Asn 
385                 390                 395                 400 


Leu His Gln Tyr Thr Phe Leu Phe Asn Glu Phe Gly Glu Gly Arg His 
                405                 410                 415     


Ala Ile Arg Phe Gln Lys Leu Leu Thr Val Glu Asp Gly Val Ala Lys 
            420                 425                 430         


Glu Val Asp Asp Val Thr Val Pro Ile Ser Met Ser Ala Gln Leu Asp 
        435                 440                 445             


Asp Leu Leu Pro Arg Asp Pro His Glu Leu Val Ala Leu Tyr Phe Gln 
    450                 455                 460                 


Asp Tyr Gly Ala Glu Gln His Leu Ala Gly Glu Phe Gly Gly Ala Lys 
465                 470                 475                 480 


Ile Gln Tyr Arg Arg Asp Gln Leu Asn His Leu His Ala Arg Arg Gly 
                485                 490                 495     


Ala Arg Asp Val Tyr Leu Asn Leu Ser Val Arg Val Gln Ser Gln Ser 
            500                 505                 510         


Glu Ala Arg Gly Glu Arg Arg Pro Pro Tyr Ala Ala Val Phe Arg Leu 
        515                 520                 525             


Val Gly Asp Asn His Arg Ala Phe Val His Phe Asp Lys Leu Ser Asp 
    530                 535                 540                 


Tyr Leu Ala Glu His Pro Asp Asp Gly Lys Leu Gly Ser Glu Gly Leu 
545                 550                 555                 560 


Leu Ser Gly Leu Arg Val Met Ser Val Ala Leu Gly Leu Arg Thr Ser 
                565                 570                 575     


Ala Ser Ile Ser Val Phe Arg Val Ala Arg Lys Asp Glu Leu Lys Pro 
            580                 585                 590         


Asn Ser Glu Gly Arg Val Pro Phe Cys Phe Pro Ile Glu Gly Asn Glu 
        595                 600                 605             


Asn Leu Val Ala Val His Glu Arg Ser Gln Leu Leu Lys Leu Pro Gly 
    610                 615                 620                 


Glu Thr Glu Ser Lys Asp Leu Arg Ala Ile Arg Glu Glu Arg Gln Arg 
625                 630                 635                 640 


Thr Leu Arg Gln Leu Arg Thr Gln Leu Ala Tyr Leu Arg Leu Leu Val 
                645                 650                 655     


Arg Cys Gly Ser Glu Asp Val Gly Arg Arg Glu Arg Ser Trp Ala Lys 
            660                 665                 670         


Leu Ile Glu Gln Pro Met Asp Ala Asn Gln Met Thr Pro Asp Trp Arg 
        675                 680                 685             


Glu Ala Phe Glu Asp Glu Leu Gln Lys Leu Lys Ser Leu Tyr Gly Ile 
    690                 695                 700                 


Cys Gly Asp Arg Glu Trp Thr Glu Ala Val Tyr Glu Ser Val Arg Arg 
705                 710                 715                 720 


Val Trp Arg His Met Gly Lys Gln Val Arg Asp Trp Arg Lys Asp Val 
                725                 730                 735     


Arg Ser Gly Glu Arg Pro Lys Ile Arg Gly Tyr Gln Lys Asp Val Val 
            740                 745                 750         


Gly Gly Asn Ser Ile Glu Gln Ile Glu Tyr Leu Glu Arg Gln Tyr Lys 
        755                 760                 765             


Phe Leu Lys Ser Trp Ser Phe Phe Gly Lys Val Ser Gly Gln Val Ile 
    770                 775                 780                 


Arg Ala Glu Lys Gly Ser Arg Phe Ala Ile Thr Leu Arg Glu His Ile 
785                 790                 795                 800 


Asp His Ala Lys Glu Asp Arg Leu Lys Lys Leu Ala Asp Arg Ile Ile 
                805                 810                 815     


Met Glu Ala Leu Gly Tyr Val Tyr Ala Leu Asp Asp Glu Arg Gly Lys 
            820                 825                 830         


Gly Lys Trp Val Ala Lys Tyr Pro Pro Cys Gln Leu Ile Leu Leu Glu 
        835                 840                 845             


Glu Leu Ser Glu Tyr Gln Phe Asn Asn Asp Arg Pro Pro Ser Glu Asn 
    850                 855                 860                 


Asn Gln Leu Met Gln Trp Ser His Arg Gly Val Phe Gln Glu Leu Leu 
865                 870                 875                 880 


Asn Gln Ala Gln Val His Asp Leu Leu Val Gly Thr Met Tyr Ala Ala 
                885                 890                 895     


Phe Ser Ser Arg Phe Asp Ala Arg Thr Gly Ala Pro Gly Ile Arg Cys 
            900                 905                 910         


Arg Arg Val Pro Ala Arg Cys Ala Arg Glu Gln Asn Pro Glu Pro Phe 
        915                 920                 925             


Pro Trp Trp Leu Asn Lys Phe Val Ala Glu His Lys Leu Asp Gly Cys 
    930                 935                 940                 


Pro Leu Arg Ala Asp Asp Leu Ile Pro Thr Gly Glu Gly Glu Phe Phe 
945                 950                 955                 960 


Val Ser Pro Phe Ser Ala Glu Glu Gly Asp Phe His Gln Ile His Ala 
                965                 970                 975     


Asp Leu Asn Ala Ala Gln Asn Leu Gln Arg Arg Leu Trp Ser Asp Phe 
            980                 985                 990         


Asp Ile Ser Gln Ile Arg Leu Arg  Cys Asp Trp Gly Glu  Val Asp Gly 
        995                 1000                 1005             


Glu Pro  Val Leu Ile Pro Arg  Thr Thr Gly Lys Arg  Thr Ala Asp 
    1010                 1015                 1020             


Ser Tyr  Gly Asn Lys Val Phe  Tyr Thr Lys Thr Gly  Val Thr Tyr 
    1025                 1030                 1035             


Tyr Glu  Arg Glu Arg Gly Lys  Lys Arg Arg Lys Val  Phe Ala Gln 
    1040                 1045                 1050             


Glu Glu  Leu Ser Glu Glu Glu  Ala Glu Leu Leu Val  Glu Ala Asp 
    1055                 1060                 1065             


Glu Ala  Arg Glu Lys Ser Val  Val Leu Met Arg Asp  Pro Ser Gly 
    1070                 1075                 1080             


Ile Ile  Asn Arg Gly Asp Trp  Thr Arg Gln Lys Glu  Phe Trp Ser 
    1085                 1090                 1095             


Met Val  Asn Gln Arg Ile Glu  Gly Tyr Leu Val Lys  Gln Ile Arg 
    1100                 1105                 1110             


Ser Arg  Val Arg Leu Gln Glu  Ser Ala Cys Glu Asn  Thr Gly Asp 
    1115                 1120                 1125             


Ile 
    


<210>  59
<211>  1258
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence dCas12d15

<400>  59

Met Asn Glu Lys Lys Thr Ala Thr Gln Arg Arg Asn Ala Arg Arg Arg 
1               5                   10                  15      


Arg Gly Glu Arg Ala Arg Thr Lys Ser Gln Glu Leu Arg Gly Tyr Arg 
            20                  25                  30          


Leu His Asp Ala Arg Ile Glu Phe Ser Gly Gly Leu Gly Ser Met Arg 
        35                  40                  45              


Thr Val Lys Val Glu Leu Leu Asn Pro Asp Ser Ser Arg Glu Asp Pro 
    50                  55                  60                  


Gln Arg Gly Gln Gly Leu Gln Gly Lys Val Ala Lys Ala Val Phe Asp 
65                  70                  75                  80  


Asp Tyr Arg Ala Leu Tyr Gly Pro Met Asn Ile Glu Asp Tyr Leu Ser 
                85                  90                  95      


Asp Pro Asp Cys Pro Ser Phe Leu Gly Leu Trp Val Lys Ala Val Cys 
            100                 105                 110         


Leu Gly Val Ile Met Ser Arg Lys Thr Ala Thr Asp Phe Gly Glu Leu 
        115                 120                 125             


Arg Gly Gly Ser Lys Ser Gly Gln Ala Phe Asp Ser Ile Pro Glu His 
    130                 135                 140                 


Leu Arg Arg Gln Leu Ile Lys Leu Lys Trp Leu Asp Trp Tyr Asp Lys 
145                 150                 155                 160 


Gly Ile Arg Lys Ser Ser Ser Lys Ala Ser Arg Leu Lys Ser Leu Thr 
                165                 170                 175     


Asp Val Phe Ala Asn Pro Lys Gln Pro Asp Gln Gly Val Met Ala Ala 
            180                 185                 190         


Trp Glu Gln Gly Glu Lys Leu Ala Glu Ser Ser Arg Asp Ile Ala Ala 
        195                 200                 205             


Leu Gly Arg Arg Glu Phe Lys Asp Lys Leu Phe Ala Ile Pro Pro Pro 
    210                 215                 220                 


Thr Ser Ser Val Val Leu Asp Asp Asp Val Lys Ala Thr Lys Val Ser 
225                 230                 235                 240 


Arg Asp Trp Gln Trp Ala Val Asp Pro Gln Phe Lys Leu Pro Ser Thr 
                245                 250                 255     


Asp Leu Asp Ile Thr Arg Ala Leu Glu Glu Val Asp Arg Gln Trp Phe 
            260                 265                 270         


Glu Arg Leu Gly Asn Asn Arg Gly Met Val Gln Gln Phe Phe Ala Ile 
        275                 280                 285             


Gly Asp Asn Gly Asn His Leu Asn Asn Gly Leu Phe Gly His Phe Phe 
    290                 295                 300                 


Ala Ser Ile Arg Ser Ala Asn Leu Ala Asp Ile Val Ala Glu Met Gly 
305                 310                 315                 320 


Thr Ala Phe Gly Phe Ser Ala Glu Glu Arg Asp Ile Val Arg Gln Arg 
                325                 330                 335     


Leu Glu Thr Leu His Glu Tyr Ala Gln Gly Leu Pro Glu Lys Pro Val 
            340                 345                 350         


Leu Ala Ser Arg Trp Ala Glu Tyr Arg Thr Asp Met Thr Ala Lys Leu 
        355                 360                 365             


Gly Ser Trp Tyr Ser Asn Arg Thr Ser Lys Gly Ala Ala Ser Ile Thr 
    370                 375                 380                 


Gln Val Trp Gly Thr Ile Asn Thr Glu Thr Gly Glu Val Lys Asp Asp 
385                 390                 395                 400 


Gly Leu Val Arg Thr Leu Glu Asn Ile Gln Ser Asp Leu Pro Asp Ser 
                405                 410                 415     


Cys Ser Ile Lys Glu Gly Ile Leu Gln Glu Thr Leu Asp Phe Ile Gly 
            420                 425                 430         


Asp Arg Arg Ser Ser Thr Asp Arg Ala Phe Thr Asp Glu Leu Glu Leu 
        435                 440                 445             


Tyr Leu Ala Thr Leu Arg Ser Asp Leu Asn Thr Trp Cys Gln Glu Gln 
    450                 455                 460                 


Ser Ala Leu Trp Glu Glu Lys Gln Arg Gln Val Ala Thr Pro Ala Ser 
465                 470                 475                 480 


Asp Glu Lys Ser Lys Lys Ala Asp Asn Pro Trp Ala Gly Lys Gly Ser 
                485                 490                 495     


Lys Thr Asp Lys Trp Leu Gly Ala Leu His Thr Arg Ile Gln Ser Ser 
            500                 505                 510         


Pro Leu Phe Trp Gly Val Asp Lys Leu Glu Leu Trp Lys Thr Leu Ala 
        515                 520                 525             


Asn Leu Lys Gln Ala Ile Arg Asp Glu Ile Asp Lys Leu Asn Glu Gln 
    530                 535                 540                 


Val Glu Val Phe Gly Arg Ser Ala Tyr Asp Glu Pro Val Gly Lys Asp 
545                 550                 555                 560 


Ala Asp Ser Gly Glu Gly Asp Arg Arg Val Asp Gln Leu Ser Tyr Leu 
                565                 570                 575     


Ser Ala Arg Leu Gly Asp Gln Ala His Glu Glu Val Arg Gln Arg Leu 
            580                 585                 590         


Asp Ala Ile Ala Leu Ala Leu Gly Val Lys Phe Ser Glu Arg Asp Asp 
        595                 600                 605             


Leu His Arg Phe Phe Val Ser Ser Arg Ala Arg Arg Arg Ala Ala Leu 
    610                 615                 620                 


Leu Ala Met Pro Asn Thr Ile Thr Val Gly Lys Leu Arg Glu Leu Ala 
625                 630                 635                 640 


Asp Leu Thr Pro Leu Trp Glu Arg Ile Lys Lys Lys Pro Glu Glu Pro 
                645                 650                 655     


Arg Leu Leu Ala Asp Thr Val Ala Leu Ser Lys Val Val Asn Ser Ala 
            660                 665                 670         


Cys Ala Ser Arg Ala Asn Pro Ser Asp Gln Ile Glu Leu Thr Thr Ile 
        675                 680                 685             


His Ser Arg Leu Asp Gly Tyr Ser Lys Asn Ile Gly His Thr Glu Phe 
    690                 695                 700                 


Ile Ser Arg Ala Thr Val Gln Ser Thr Asn Gly Ala Gln Asn Thr Val 
705                 710                 715                 720 


Ala Leu Asp Ser Leu Val Ser Pro Arg Leu Phe Tyr Tyr Asn Phe Pro 
                725                 730                 735     


Asn Ile Val Glu Ser Ala Glu Pro His Val Ser His Leu Glu Val Ala 
            740                 745                 750         


Thr Arg Gly Asn Leu Gly Ser Phe Glu Glu Phe Ala Ala Lys Glu His 
        755                 760                 765             


Arg Thr Phe Asp Arg Glu Asn Pro Gln Lys Asp Ser Arg Asn Arg Ile 
    770                 775                 780                 


Asp Ser Val Asn Pro Leu Ala Val Ala Ser Ser Arg Tyr Gln Ile Gln 
785                 790                 795                 800 


Phe Phe Thr Trp Trp Ala Gly Leu His Arg Ser Lys Glu Thr Ala Leu 
                805                 810                 815     


Glu Val Gly Gly Ser Phe Thr Ile Ala Glu Arg Gln Val Arg Leu Asp 
            820                 825                 830         


Trp Ser Gln Glu Lys Pro Gln Ala Val Val Ser Glu Glu Leu Arg Val 
        835                 840                 845             


Phe Val Ser Gln Pro Phe Thr Ile Val Pro Asp Asp Lys Lys Arg Pro 
    850                 855                 860                 


Ala Thr Ser Gly Thr Arg Tyr Ile Gly Val Ala Ile Gly Glu Tyr Gly 
865                 870                 875                 880 


Leu Ala Trp Ser Cys Trp Glu Phe Ala Pro Gly Tyr Trp Asn Gly Ser 
                885                 890                 895     


Val Val Asn Pro Ser Lys Val Thr Cys Leu Asp Tyr Gly Phe Leu Ala 
            900                 905                 910         


Glu Pro Gly Gln Arg Arg Ile Val Glu Arg Val Lys Lys Leu Arg Glu 
        915                 920                 925             


Ser Gln Ala Thr Lys Thr Phe Thr Ser Pro Asp Thr Tyr Ile Ala Arg 
    930                 935                 940                 


Leu Arg Glu Asn Val Val Ala Thr Tyr Gln Ala Gln Leu Glu Ala Leu 
945                 950                 955                 960 


Met Met Ala Tyr Asn Ala Gln Leu Val Phe Ala Ser Glu Ile Ser Ala 
                965                 970                 975     


Phe Glu Thr Gly Gly Asn Arg Val Lys Lys Ile Tyr Asp Ala Ile Lys 
            980                 985                 990         


Arg Ser Ser Val Phe Gly Arg Ser  Asp Ala Glu Ala Thr  Asp Asn Asn 
        995                 1000                 1005             


Gln His  Trp Gly Lys Asn Gly  Asn Arg Ser Ser Val  Lys Asp Pro 
    1010                 1015                 1020             


Asp Lys  Leu Arg Leu Asn Glu  Ala Gly Gln Val Ala  Ala Arg Val 
    1025                 1030                 1035             


Pro Trp  Ala Glu Pro Val Ser  Ala Trp Met Thr Ser  Gln Thr Cys 
    1040                 1045                 1050             


Ser Ala  Cys Gly Arg Val Tyr  Val Arg Ala Tyr Arg  Gly Lys Asn 
    1055                 1060                 1065             


Ser Asn  Glu Pro Asp Ser Gly  Ala Thr Gly Glu Val  Arg Tyr Phe 
    1070                 1075                 1080             


Asp Asn  Lys Gln Gln Lys Ile  Leu Thr Lys Thr Ile  Gly Ala Asp 
    1085                 1090                 1095             


Thr Val  Trp Val Thr Asp Gln  Glu Arg Lys Glu Phe  Glu Arg Gly 
    1100                 1105                 1110             


Val Tyr  Asn Ala Met Arg Pro  Asn Ala Phe Met Pro  Asp Gly Arg 
    1115                 1120                 1125             


Trp Thr  Ala Ala Gly Glu Ile  Leu Glu Ala Ala Leu  Lys Ser Arg 
    1130                 1135                 1140             


Gly Thr  Leu Asp Gly Gly Arg  Gly Phe Ala Gly Leu  His Leu Thr 
    1145                 1150                 1155             


Ser Lys  Ala Gln Val His Glu  Tyr Ile Glu Gly Thr  Gly Lys Ser 
    1160                 1165                 1170             


His Arg  Asp Ala His Gly Asn  Ser Ala Ile Phe Ile  Cys Pro Tyr 
    1175                 1180                 1185             


Thr Asp  Cys Gly His Ile Ala  Asp Ala Ala Leu Gln  Ala Ser Tyr 
    1190                 1195                 1200             


Asn Ile  Ala Leu Arg Gly Phe  Ala Tyr Ala Ile Val  Arg Lys Lys 
    1205                 1210                 1215             


His Pro  Glu Leu Phe Ala Gly  Ser Gly Ser Ser Thr  Asp Gly Asp 
    1220                 1225                 1230             


Glu Gly  Gly Gly Lys Lys Pro  Gln Gln Lys Gln Ala  Phe Ile Asp 
    1235                 1240                 1245             


Glu Ile  Val Arg Ala Ala Gly  Arg Ala Ser 
    1250                 1255             


<210>  60
<211>  84
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Bacillus phage PBS2 Uracil-DNA glycosylase inhibitor

<400>  60

Met Thr Asn Leu Ser Asp Ile Ile Glu Lys Glu Thr Gly Lys Gln Leu 
1               5                   10                  15      


Val Ile Gln Glu Ser Ile Leu Met Leu Pro Glu Glu Val Glu Glu Val 
            20                  25                  30          


Ile Gly Asn Lys Pro Glu Ser Asp Ile Leu Val His Thr Ala Tyr Asp 
        35                  40                  45              


Glu Ser Thr Asp Glu Asn Val Met Leu Leu Thr Ser Asp Ala Pro Glu 
    50                  55                  60                  


Tyr Lys Pro Trp Ala Leu Val Ile Gln Asp Ser Asn Gly Glu Asn Lys 
65                  70                  75                  80  


Ile Lys Met Leu 
                


<210>  61
<211>  93
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Hybrid Type II crRNA:tracrRNA guide RNA sequence

<400>  61
guuuaagagc uaugcuggaa acagcauagc aaguuuaaau aaggcuaguc cguuaucaac       60

uugaaaaagu ggcaccgagu cggugcuuuu uuu                                    93


<210>  62
<211>  129
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RNA scaffold expression cassette (S. pyogenes), containing a 
       20-nucleotide programmable sequence, a CRISPR RNA motif, and an 
       MS2 operator motif


<220>
<221>  misc_feature
<222>  (1)..(20)
<223>  n is a, c, g, or t

<400>  62
nnnnnnnnnn nnnnnnnnnn gttttagagc tagaaatagc aagttaaaat aaggctagtc       60

cgttatcaac ttgaaaaagt ggcaccgagt cggtgcgcgc acatgaggat cacccatgtg      120

ctttttttg                                                              129


<210>  63
<211>  157
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RNA scaffold containing two MS2 loops (2xMS2)

<400>  63
gttttagagc tagaaatagc aagttaaaat aaggctagtc cgttatcaac ttgaaaaagt       60

ggcaccgagt cggtgcggga gcacatgagg atcacccatg tgccacgagc gacatgagga      120

tcacccatgt cgctcgtgtt cccttttttt ctccgct                               157


<210>  64
<211>  957
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  NLS-Anolis(P16A-E17A)-Apobec1-Linker-MCP RNA seq

<400>  64
auggccccca agaagaagcg gaaagugaug gagccggagg cuuuucagcg caacuuugac       60

ccucgggaau uugccgccug uacacuccuc uuguaugaga uccacuggga caauaacaca      120

ucuagaaauu gguguacgaa uaagccuggg cuccacgcug aggagaauuu cuugcagaua      180

uuuaaugaga aaauugacau uaaacaggau acgccgugcu cuauaacaug guuccuuucu      240

uggagccccu guuacccuug uagccaagca auaauaaaau ucuuggaggc acacccgaau      300

gucagucugg agauuaaggc ugcgcggcug uauaugcauc aaauagacug uaacaaggag      360

ggacucagaa aucugggccg gaaucgagug ucaauaauga accugccuga uuauaggcau      420

ugcuggacua cguuuguugu gccaagggga gcaaacgaag auuacuggcc acaagacuuu      480

cugccugcga ucacaaauua cucccgagaa cucgacucca uacugcagga ugagcugaag      540

acaccccugg gcgacaccac acacaccucu ccaccuugcc cagcaccaga gcugcuggga      600

ggcccuaugg ccagcaacuu cacacaguuu gugcuggugg auaauggagg aaccggcgac      660

gugacagugg caccaucuaa cuuugccaau ggcaucgccg aguggaucag cuccaacucu      720

cggagccagg ccuauaaggu gaccuguagc gugcggcagu cuagcgccca gaauagaaag      780

uauacaauca agguggaggu gccuaagggc gccuggagau ccuaccugaa cauggagcug      840

accaucccaa ucuuugccac aaauucugau ugcgagcuga ucgugaaggc caugcagggc      900

cugcugaagg acggcaaccc uaucccaagc gccaucgccg ccaauagcgg aaucuac         957


<210>  65
<211>  1137
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  NLS-Rattus-Apobec1-Linker-MCP RNA seq

<400>  65
auggccccca agaagaagcg gaaagugucc ucagagacug ggccugucgc cgucgaucca       60

acccugcgcc gccggauuga accucacgag uuugaagugu ucuuugaccc ccgggagcug      120

agaaaggaga caugccugcu guacgagauc aacuggggag gcaggcacuc caucuggagg      180

cacaccucuc agaacacaaa uaagcacgug gaggugaacu ucaucgagaa guuuaccaca      240

gagcgguacu ucugccccaa uaccagaugu agcaucacau gguuucugag cugguccccu      300

ugcggagagu guagcagggc caucaccgag uuccugucca gauauccaca cgugacacug      360

uuuaucuaca ucgccaggcu guaucaccac gcagacccaa ggaauaggca gggccugcgc      420

gaucugauca gcuccggcgu gaccauccag aucaugacag agcaggaguc cggcuacugc      480

uggcggaacu ucgugaauua uucuccuagc aacgaggccc acuggccuag guacccacac      540

cugugggugc gccuguacgu gcuggagcug uauugcauca uccugggccu gcccccuugu      600

cugaauaucc ugcggagaaa gcagccccag cugaccuucu uuacaaucgc ccugcagucu      660

ugucacuauc agaggcugcc accccacauc cugugggcca caggccugaa ggagcugaag      720

acaccccugg gcgacaccac acacaccucu ccaccuugcc cagcaccaga gcugcuggga      780

ggcccuaugg ccagcaacuu cacacaguuu gugcuggugg auaauggagg aaccggcgac      840

gugacagugg caccaucuaa cuuugccaau ggcaucgccg aguggaucag cuccaacucu      900

cggagccagg ccuauaaggu gaccuguagc gugcggcagu cuagcgccca gaauagaaag      960

uauacaauca agguggaggu gccuaagggc gccuggagau ccuaccugaa cauggagcug     1020

accaucccaa ucuuugccac aaauucugau ugcgagcuga ucgugaaggc caugcagggc     1080

cugcugaagg acggcaaccc uaucccaagc gccaucgccg ccaauagcgg aaucuac        1137


<210>  66
<211>  1047
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  NLS-Homo-AID-L25-MCP RNA seq

<400>  66
auggccccca agaagaagcg gaaagugaug gauagccugc ugaugaaccg gagaaaguuc       60

cuguaucagu uuaagaaugu gcgcugggca aagggcaggc gcgagaccua ccugugcuau      120

guggugaagc ggagagauuc cgccacaucc uucucucugg acuuuggcua ccugcggaac      180

aagaauggcu gccacgugga gcugcuguuc cugagauaca ucucugacug ggaucuggac      240

ccaggcaggu guuaucgcgu gaccugguuc acaagcuggu cccccugcua cgauugugca      300

aggcacgugg cagacuuucu gaggggaaac ccaaaucugu cccugcggau cuucaccgcc      360

agacuguauu uuugcgagga uaggaaggca gagccagagg gacugaggcg ccugcacagg      420

gccggcgugc agaucgccau caugaccuuc aaggacuacu uuuauuguug gaacaccuuc      480

guggagaauc acgagcggac cuucaaggcc ugggagggac ugcacgagaa cuccgugcgg      540

cugucuagac agcugcggag aauccugcug ccucuguacg agguggacga ucugagggau      600

gccuuccgca cccugggacu ggagcugaag acaccccugg gcgacaccac acacaccucu      660

ccaccuugcc cagcaccaga gcugcuggga ggcccuaugg ccagcaacuu cacacaguuu      720

gugcuggugg auaauggagg aaccggcgac gugacagugg caccaucuaa cuuugccaau      780

ggcaucgccg aguggaucag cuccaacucu cggagccagg ccuauaaggu gaccuguagc      840

gugcggcagu cuagcgccca gaauagaaag uauacaauca agguggaggu gccuaagggc      900

gccuggagau ccuaccugaa cauggagcug accaucccaa ucuuugccac aaauucugau      960

ugcgagcuga ucgugaaggc caugcagggc cugcugaagg acggcaaccc uaucccaagc     1020

gccaucgccg ccaauagcgg aaucuac                                         1047


<210>  67
<211>  4746
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  NLS-nCas9(D10A)-UGI-UGI-NLS RNA seq

<400>  67
augccaaaga agaagcggaa agucgacaag aaguacagca ucggccuggc caucggcacc       60

aacucugugg gcugggccgu gaucaccgac gaguacaagg ugcccagcaa gaaauucaag      120

gugcugggca acaccgaccg gcacagcauc aagaagaacc ugaucggagc ccugcuguuc      180

gacagcggcg aaacagccga ggccacccgg cugaagagaa ccgccagaag aagauacacc      240

agacggaaga accggaucug cuaucugcaa gagaucuuca gcaacgagau ggccaaggug      300

gacgacagcu ucuuccacag acuggaagag uccuuccugg uggaagagga uaagaagcac      360

gagcggcacc ccaucuucgg caacaucgug gacgaggugg ccuaccacga gaaguacccc      420

accaucuacc accugagaaa gaaacuggug gacagcaccg acaaggccga ccugcggcug      480

aucuaucugg cccuggccca caugaucaag uuccggggcc acuuccugau cgagggcgac      540

cugaaccccg acaacagcga cguggacaag cuguucaucc agcuggugca gaccuacaac      600

cagcuguucg aggaaaaccc caucaacgcc agcggcgugg acgccaaggc cauccugucu      660

gccagacuga gcaagagcag acggcuggaa aaucugaucg cccagcugcc cggcgagaag      720

aagaauggcc uguucggaaa ccugauugcc cugagccugg gccugacccc caacuucaag      780

agcaacuucg accuggccga ggaugccaaa cugcagcuga gcaaggacac cuacgacgac      840

gaccuggaca accugcuggc ccagaucggc gaccaguacg ccgaccuguu ucuggccgcc      900

aagaaccugu ccgacgccau ccugcugagc gacauccuga gagugaacac cgagaucacc      960

aaggcccccc ugagcgccuc uaugaucaag agauacgacg agcaccacca ggaccugacc     1020

cugcugaaag cucucgugcg gcagcagcug ccugagaagu acaaagagau uuucuucgac     1080

cagagcaaga acggcuacgc cggcuacauu gacggcggag ccagccagga agaguucuac     1140

aaguucauca agcccauccu ggaaaagaug gacggcaccg aggaacugcu cgugaagcug     1200

aacagagagg accugcugcg gaagcagcgg accuucgaca acggcagcau cccccaccag     1260

auccaccugg gagagcugca cgccauucug cggcggcagg aagauuuuua cccauuccug     1320

aaggacaacc gggaaaagau cgagaagauc cugaccuucc gcauccccua cuacgugggc     1380

ccucuggcca ggggaaacag cagauucgcc uggaugacca gaaagagcga ggaaaccauc     1440

acccccugga acuucgagga agugguggac aagggcgcuu ccgcccagag cuucaucgag     1500

cggaugacca acuucgauaa gaaccugccc aacgagaagg ugcugcccaa gcacagccug     1560

cuguacgagu acuucaccgu guauaacgag cugaccaaag ugaaauacgu gaccgaggga     1620

augagaaagc ccgccuuccu gagcggcgag cagaaaaagg ccaucgugga ccugcuguuc     1680

aagaccaacc ggaaagugac cgugaagcag cugaaagagg acuacuucaa gaaaaucgag     1740

ugcuucgacu ccguggaaau cuccggcgug gaagaucggu ucaacgccuc ccugggcaca     1800

uaccacgauc ugcugaaaau uaucaaggac aaggacuucc uggacaauga ggaaaacgag     1860

gacauucugg aagauaucgu gcugacccug acacuguuug aggacagaga gaugaucgag     1920

gaacggcuga aaaccuaugc ccaccuguuc gacgacaaag ugaugaagca gcugaagcgg     1980

cggagauaca ccggcugggg caggcugagc cggaagcuga ucaacggcau ccgggacaag     2040

caguccggca agacaauccu ggauuuccug aaguccgacg gcuucgccaa cagaaacuuc     2100

augcagcuga uccacgacga cagccugacc uuuaaagagg acauccagaa agcccaggug     2160

uccggccagg gcgauagccu gcacgagcac auugccaauc uggccggcag ccccgccauu     2220

aagaagggca uccugcagac agugaaggug guggacgagc ucgugaaagu gaugggccgg     2280

cacaagcccg agaacaucgu gaucgaaaug gccagagaga accagaccac ccagaaggga     2340

cagaagaaca gccgcgagag aaugaagcgg aucgaagagg gcaucaaaga gcugggcagc     2400

cagauccuga aagaacaccc cguggaaaac acccagcugc agaacgagaa gcuguaccug     2460

uacuaccugc agaaugggcg ggauauguac guggaccagg aacuggacau caaccggcug     2520

uccgacuacg auguggacca uaucgugccu cagagcuuuc ugaaggacga cuccaucgac     2580

aacaaggugc ugaccagaag cgacaagaac cggggcaaga gcgacaacgu gcccuccgaa     2640

gaggucguga agaagaugaa gaacuacugg cggcagcugc ugaacgccaa gcugauuacc     2700

cagagaaagu ucgacaaucu gaccaaggcc gagagaggcg gccugagcga acuggauaag     2760

gccggcuuca ucaagagaca gcugguggaa acccggcaga ucacaaagca cguggcacag     2820

auccuggacu cccggaugaa cacuaaguac gacgagaaug acaagcugau ccgggaagug     2880

aaagugauca cccugaaguc caagcuggug uccgauuucc ggaaggauuu ccaguuuuac     2940

aaagugcgcg agaucaacaa cuaccaccac gcccacgacg ccuaccugaa cgccgucgug     3000

ggaaccgccc ugaucaaaaa guacccuaag cuggaaagcg aguucgugua cggcgacuac     3060

aagguguacg acgugcggaa gaugaucgcc aagagcgagc aggaaaucgg caaggcuacc     3120

gccaaguacu ucuucuacag caacaucaug aacuuuuuca agaccgagau uacccuggcc     3180

aacggcgaga uccggaagcg gccucugauc gagacaaacg gcgaaaccgg ggagaucgug     3240

ugggauaagg gccgggauuu ugccaccgug cggaaagugc ugagcaugcc ccaagugaau     3300

aucgugaaaa agaccgaggu gcagacaggc ggcuucagca aagagucuau ccugcccaag     3360

aggaacagcg auaagcugau cgccagaaag aaggacuggg acccuaagaa guacggcggc     3420

uucgacagcc ccaccguggc cuauucugug cugguggugg ccaaagugga aaagggcaag     3480

uccaagaaac ugaagagugu gaaagagcug cuggggauca ccaucaugga aagaagcagc     3540

uucgagaaga aucccaucga cuuucuggaa gccaagggcu acaaagaagu gaaaaaggac     3600

cugaucauca agcugccuaa guacucccug uucgagcugg aaaacggccg gaagagaaug     3660

cuggccucug ccggcgaacu gcagaaggga aacgaacugg cccugcccuc caaauaugug     3720

aacuuccugu accuggccag ccacuaugag aagcugaagg gcucccccga ggauaaugag     3780

cagaaacagc uguuugugga acagcacaag cacuaccugg acgagaucau cgagcagauc     3840

agcgaguucu ccaagagagu gauccuggcc gacgcuaauc uggacaaagu gcuguccgcc     3900

uacaacaagc accgggauaa gcccaucaga gagcaggccg agaauaucau ccaccuguuu     3960

acccugacca aucugggagc cccugccgcc uucaaguacu uugacaccac caucgaccgg     4020

aagagguaca ccagcaccaa agaggugcug gacgccaccc ugauccacca gagcaucacc     4080

ggccuguacg agacacggau cgaccugucu cagcugggag gugacagcgg cgggagcggc     4140

gggagcgggg ggagcacuaa ucugagcgac aucauugaga aggagacugg gaaacagcug     4200

gucauucagg aguccauccu gaugcugccu gaggaggugg aggaagugau cggcaacaag     4260

ccagagucug acauccuggu gcacaccgcc uacgacgagu ccacagauga gaaugugaug     4320

cugcugaccu cugacgcccc cgaguauaag ccuugggccc uggucaucca ggauucuaac     4380

ggcgagaaua agaucaagau gcugagcgga ggauccggag gaucuggagg cagcaccaac     4440

cugucugaca ucaucgagaa ggagacaggc aagcagcugg ucauccagga gagcauccug     4500

augcugcccg aagaagucga agaagugauc ggaaacaagc cugagagcga uauccugguc     4560

cauaccgccu acgacgagag uaccgacgaa aaugugaugc ugcugacauc cgacgcccca     4620

gaguauaagc ccugggcucu ggucauccag gauuccaacg gagagaacaa aaucaaaaug     4680

cugucuggcg gcucaaaaag aaccgccgac ggcagcgaau ucgagcccaa gaagaagagg     4740

aaaguc                                                                4746


<210>  68
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Qbeta phage operator stem-loop seq

<400>  68
atgctgtcta agacagcat                                                    19


<210>  69
<211>  133
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Qbeta coat protein [Q65H] seq

<400>  69

Met Ala Lys Leu Glu Thr Val Thr Leu Gly Asn Ile Gly Lys Asp Gly 
1               5                   10                  15      


Lys Gln Thr Leu Val Leu Asn Pro Arg Gly Val Asn Pro Thr Asn Gly 
            20                  25                  30          


Val Ala Ser Leu Ser Gln Ala Gly Ala Val Pro Ala Leu Glu Lys Arg 
        35                  40                  45              


Val Thr Val Ser Val Ser Gln Pro Ser Arg Asn Arg Lys Asn Tyr Lys 
    50                  55                  60                  


Val His Val Lys Ile Gln Asn Pro Thr Ala Cys Thr Ala Asn Gly Ser 
65                  70                  75                  80  


Cys Asp Pro Ser Val Thr Arg Gln Ala Tyr Ala Asp Val Thr Phe Ser 
                85                  90                  95      


Phe Thr Gln Tyr Ser Thr Asp Glu Glu Arg Ala Phe Val Arg Thr Glu 
            100                 105                 110         


Leu Ala Ala Leu Leu Ala Ser Pro Leu Leu Ile Asp Ala Ile Asp Gln 
        115                 120                 125             


Leu Asn Pro Ala Tyr 
    130             


<210>  70
<211>  15
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  BoxB seq

<400>  70
gccctgaaga agggc                                                        15


<210>  71
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Lambda bacteriophage protein N (LambdaN-(1-22) seq

<400>  71

Met Asn Ala Arg Thr Arg Arg Arg Glu Arg Arg Ala Glu Lys Gln Ala 
1               5                   10                  15      


Gln Trp Lys Ala Ala Asn 
            20          


<210>  72
<211>  16
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Csy4 binding motif

<400>  72
ctgccgtata ggcagc                                                       16


<210>  73
<211>  187
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Csy4[H29A] seq

<400>  73

Met Asp His Tyr Leu Asp Ile Arg Leu Arg Pro Asp Pro Glu Phe Pro 
1               5                   10                  15      


Pro Ala Gln Leu Met Ser Val Leu Phe Gly Lys Leu Ala Gln Ala Leu 
            20                  25                  30          


Val Ala Gln Gly Gly Asp Arg Ile Gly Val Ser Phe Pro Asp Leu Asp 
        35                  40                  45              


Glu Ser Arg Ser Arg Leu Gly Glu Arg Leu Arg Ile His Ala Ser Ala 
    50                  55                  60                  


Asp Asp Leu Arg Ala Leu Leu Ala Arg Pro Trp Leu Glu Gly Leu Arg 
65                  70                  75                  80  


Asp His Leu Gln Phe Gly Glu Pro Ala Val Val Pro His Pro Thr Pro 
                85                  90                  95      


Tyr Arg Gln Val Ser Arg Val Gln Ala Lys Ser Asn Pro Glu Arg Leu 
            100                 105                 110         


Arg Arg Arg Leu Met Arg Arg His Asp Leu Ser Glu Glu Glu Ala Arg 
        115                 120                 125             


Lys Arg Ile Pro Asp Thr Val Ala Arg Ala Leu Asp Leu Pro Phe Val 
    130                 135                 140                 


Thr Leu Arg Ser Gln Ser Thr Gly Gln His Phe Arg Leu Phe Ile Arg 
145                 150                 155                 160 


His Gly Pro Leu Gln Val Thr Ala Glu Glu Gly Gly Phe Thr Cys Tyr 
                165                 170                 175     


Gly Leu Ser Lys Gly Gly Phe Val Pro Trp Phe 
            180                 185         


