                         SEQUENCE LISTING

<110>  Universitt Heidelberg
 
<120>  Activity-optimizing peptide

<130>  UH14671PC

<150>  EP21166099.8
<151>  2021-03-30

<160>  46    

<170>  PatentIn version 3.5

<210>  1
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  tag peptide sequence 1

<400>  1

Gln Lys Leu Ile Ser Glu Glu Asp Leu 
1               5                   


<210>  2
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  tag peptide sequence 2

<400>  2

Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 
1               5                   10  


<210>  3
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  tag-linker fusion peptide sequence

<400>  3

Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Gly Gly Ser Gly 
1               5                   10                  


<210>  4
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NLS 1

<400>  4

Pro Pro Pro Lys Arg Pro Arg Leu Asp 
1               5                   


<210>  5
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NLS 2

<400>  5

Pro Lys Lys Lys Arg Lys Val 
1               5           


<210>  6
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NLS 3

<400>  6

Arg Ala Asp Pro Lys Lys Lys Arg Lys Val 
1               5                   10  


<210>  7
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NLS 4

<400>  7

Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 
1               5                   10                  15  


<210>  8
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NLS 5

<400>  8

Ala Pro Lys Lys Lys Arg Lys Val Gly Ile His Gly Val Pro Ala Ala 
1               5                   10                  15      


<210>  9
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NLS 6

<400>  9

Pro Lys Lys Lys Arg Lys 
1               5       


<210>  10
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NLS 7

<400>  10

Ala Pro Lys Lys Lys Arg Lys 
1               5           


<210>  11
<211>  23
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  tag-linker-NLS fusion peptide (NAO peptide) sequence

<400>  11

Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Gly Gly Ser Gly Pro Pro 
1               5                   10                  15      


Pro Lys Arg Pro Arg Leu Asp 
            20              


<210>  12
<211>  1404
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HeiCas9 (MFO-Cas9-O)

<400>  12

Met Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Gly Gly Ser Gly Pro 
1               5                   10                  15      


Pro Pro Lys Arg Pro Arg Leu Asp Leu Glu Asp Lys Lys Tyr Ser Ile 
            20                  25                  30          


Gly Leu Asp Ile Gly Thr Asn Ser Val Gly Trp Ala Val Ile Thr Asp 
        35                  40                  45              


Glu Tyr Lys Val Pro Ser Lys Lys Phe Lys Val Leu Gly Asn Thr Asp 
    50                  55                  60                  


Arg His Ser Ile Lys Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp Ser 
65                  70                  75                  80  


Gly Glu Thr Ala Glu Ala Thr Arg Leu Lys Arg Thr Ala Arg Arg Arg 
                85                  90                  95      


Tyr Thr Arg Arg Lys Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe Ser 
            100                 105                 110         


Asn Glu Met Ala Lys Val Asp Asp Ser Phe Phe His Arg Leu Glu Glu 
        115                 120                 125             


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


Gly Asn Ile Val Asp Glu Val Ala Tyr His Glu Lys Tyr Pro Thr Ile 
145                 150                 155                 160 


Tyr His Leu Arg Lys Lys Leu Val Asp Ser Thr Asp Lys Ala Asp Leu 
                165                 170                 175     


Arg Leu Ile Tyr Leu Ala Leu Ala His Met Ile Lys Phe Arg Gly His 
            180                 185                 190         


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


Leu Phe Ile Gln Leu Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu Asn 
    210                 215                 220                 


Pro Ile Asn Ala Ser Gly Val Asp Ala Lys Ala Ile Leu Ser Ala Arg 
225                 230                 235                 240 


Leu Ser Lys Ser Arg Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro Gly 
                245                 250                 255     


Glu Lys Lys Asn Gly Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu Gly 
            260                 265                 270         


Leu Thr Pro Asn Phe Lys Ser Asn Phe Asp Leu Ala Glu Asp Ala Lys 
        275                 280                 285             


Leu Gln Leu Ser Lys Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu Leu 
    290                 295                 300                 


Ala Gln Ile Gly Asp Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys Asn 
305                 310                 315                 320 


Leu Ser Asp Ala Ile Leu Leu Ser Asp Ile Leu Arg Val Asn Thr Glu 
                325                 330                 335     


Ile Thr Lys Ala Pro Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp Glu 
            340                 345                 350         


His His Gln Asp Leu Thr Leu Leu Lys Ala Leu Val Arg Gln Gln Leu 
        355                 360                 365             


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


Ala Gly Tyr Ile Asp Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys Phe 
385                 390                 395                 400 


Ile Lys Pro Ile Leu Glu Lys Met Asp Gly Thr Glu Glu Leu Leu Val 
                405                 410                 415     


Lys Leu Asn Arg Glu Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp Asn 
            420                 425                 430         


Gly Ser Ile Pro His Gln Ile His Leu Gly Glu Leu His Ala Ile Leu 
        435                 440                 445             


Arg Arg Gln Glu Asp Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu Lys 
    450                 455                 460                 


Ile Glu Lys Ile Leu Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro Leu 
465                 470                 475                 480 


Ala Arg Gly Asn Ser Arg Phe Ala Trp Met Thr Arg Lys Ser Glu Glu 
                485                 490                 495     


Thr Ile Thr Pro Trp Asn Phe Glu Glu Val Val Asp Lys Gly Ala Ser 
            500                 505                 510         


Ala Gln Ser Phe Ile Glu Arg Met Thr Asn Phe Asp Lys Asn Leu Pro 
        515                 520                 525             


Asn Glu Lys Val Leu Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe Thr 
    530                 535                 540                 


Val Tyr Asn Glu Leu Thr Lys Val Lys Tyr Val Thr Glu Gly Met Arg 
545                 550                 555                 560 


Lys Pro Ala Phe Leu Ser Gly Glu Gln Lys Lys Ala Ile Val Asp Leu 
                565                 570                 575     


Leu Phe Lys Thr Asn Arg Lys Val Thr Val Lys Gln Leu Lys Glu Asp 
            580                 585                 590         


Tyr Phe Lys Lys Ile Glu Cys Phe Asp Ser Val Glu Ile Ser Gly Val 
        595                 600                 605             


Glu Asp Arg Phe Asn Ala Ser Leu Gly Thr Tyr His Asp Leu Leu Lys 
    610                 615                 620                 


Ile Ile Lys Asp Lys Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile 
625                 630                 635                 640 


Leu Glu Asp Ile Val Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu Met 
                645                 650                 655     


Ile Glu Glu Arg Leu Lys Thr Tyr Ala His Leu Phe Asp Asp Lys Val 
            660                 665                 670         


Met Lys Gln Leu Lys Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser 
        675                 680                 685             


Arg Lys Leu Ile Asn Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile 
    690                 695                 700                 


Leu Asp Phe Leu Lys Ser Asp Gly Phe Ala Asn Arg Asn Phe Met Gln 
705                 710                 715                 720 


Leu Ile His Asp Asp Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala 
                725                 730                 735     


Gln Val Ser Gly Gln Gly Asp Ser Leu His Glu His Ile Ala Asn Leu 
            740                 745                 750         


Ala Gly Ser Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val 
        755                 760                 765             


Val Asp Glu Leu Val Lys Val Met Gly Arg His Lys Pro Glu Asn Ile 
    770                 775                 780                 


Val Ile Glu Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys 
785                 790                 795                 800 


Asn Ser Arg Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu 
                805                 810                 815     


Gly Ser Gln Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln 
            820                 825                 830         


Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr 
        835                 840                 845             


Val Asp Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp 
    850                 855                 860                 


His Ile Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn Lys 
865                 870                 875                 880 


Val Leu Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn Val Pro 
                885                 890                 895     


Ser Glu Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg Gln Leu Leu 
            900                 905                 910         


Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn Leu Thr Lys Ala 
        915                 920                 925             


Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys Ala Gly Phe Ile Lys Arg 
    930                 935                 940                 


Gln Leu Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Gln Ile Leu 
945                 950                 955                 960 


Asp Ser Arg Met Asn Thr Lys Tyr Asp Glu Asn Asp Lys Leu Ile Arg 
                965                 970                 975     


Glu Val Lys Val Ile Thr Leu Lys Ser Lys Leu Val Ser Asp Phe Arg 
            980                 985                 990         


Lys Asp Phe Gln Phe Tyr Lys Val  Arg Glu Ile Asn Asn  Tyr His His 
        995                 1000                 1005             


Ala His  Asp Ala Tyr Leu Asn  Ala Val Val Gly Thr  Ala Leu Ile 
    1010                 1015                 1020             


Lys Lys  Tyr Pro Lys Leu Glu  Ser Glu Phe Val Tyr  Gly Asp Tyr 
    1025                 1030                 1035             


Lys Val  Tyr Asp Val Arg Lys  Met Ile Ala Lys Ser  Glu Gln Glu 
    1040                 1045                 1050             


Ile Gly  Lys Ala Thr Ala Lys  Tyr Phe Phe Tyr Ser  Asn Ile Met 
    1055                 1060                 1065             


Asn Phe  Phe Lys Thr Glu Ile  Thr Leu Ala Asn Gly  Glu Ile Arg 
    1070                 1075                 1080             


Lys Arg  Pro Leu Ile Glu Thr  Asn Gly Glu Thr Gly  Glu Ile Val 
    1085                 1090                 1095             


Trp Asp  Lys Gly Arg Asp Phe  Ala Thr Val Arg Lys  Val Leu Ser 
    1100                 1105                 1110             


Met Pro  Gln Val Asn Ile Val  Lys Lys Thr Glu Val  Gln Thr Gly 
    1115                 1120                 1125             


Gly Phe  Ser Lys Glu Ser Ile  Leu Pro Lys Arg Asn  Ser Asp Lys 
    1130                 1135                 1140             


Leu Ile  Ala Arg Lys Lys Asp  Trp Asp Pro Lys Lys  Tyr Gly Gly 
    1145                 1150                 1155             


Phe Asp  Ser Pro Thr Val Ala  Tyr Ser Val Leu Val  Val Ala Lys 
    1160                 1165                 1170             


Val Glu  Lys Gly Lys Ser Lys  Lys Leu Lys Ser Val  Lys Glu Leu 
    1175                 1180                 1185             


Leu Gly  Ile Thr Ile Met Glu  Arg Ser Ser Phe Glu  Lys Asn Pro 
    1190                 1195                 1200             


Ile Asp  Phe Leu Glu Ala Lys  Gly Tyr Lys Glu Val  Lys Lys Asp 
    1205                 1210                 1215             


Leu Ile  Ile Lys Leu Pro Lys  Tyr Ser Leu Phe Glu  Leu Glu Asn 
    1220                 1225                 1230             


Gly Arg  Lys Arg Met Leu Ala  Ser Ala Gly Glu Leu  Gln Lys Gly 
    1235                 1240                 1245             


Asn Glu  Leu Ala Leu Pro Ser  Lys Tyr Val Asn Phe  Leu Tyr Leu 
    1250                 1255                 1260             


Ala Ser  His Tyr Glu Lys Leu  Lys Gly Ser Pro Glu  Asp Asn Glu 
    1265                 1270                 1275             


Gln Lys  Gln Leu Phe Val Glu  Gln His Lys His Tyr  Leu Asp Glu 
    1280                 1285                 1290             


Ile Ile  Glu Gln Ile Ser Glu  Phe Ser Lys Arg Val  Ile Leu Ala 
    1295                 1300                 1305             


Asp Ala  Asn Leu Asp Lys Val  Leu Ser Ala Tyr Asn  Lys His Arg 
    1310                 1315                 1320             


Asp Lys  Pro Ile Arg Glu Gln  Ala Glu Asn Ile Ile  His Leu Phe 
    1325                 1330                 1335             


Thr Leu  Thr Asn Leu Gly Ala  Pro Ala Ala Phe Lys  Tyr Phe Asp 
    1340                 1345                 1350             


Thr Thr  Ile Asp Arg Lys Arg  Tyr Thr Ser Thr Lys  Glu Val Leu 
    1355                 1360                 1365             


Asp Ala  Thr Leu Ile His Gln  Ser Ile Thr Gly Leu  Tyr Glu Thr 
    1370                 1375                 1380             


Arg Ile  Asp Leu Ser Gln Leu  Gly Gly Asp Gly Ser  Pro Pro Pro 
    1385                 1390                 1395             


Lys Arg  Pro Arg Leu Asp 
    1400                 


<210>  13
<211>  1406
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  MIS-Cas9-S

<400>  13

Met Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Gly Ile His Gly Val 
1               5                   10                  15      


Pro Ala Ala Ala Pro Lys Lys Lys Arg Lys Val Asp Lys Lys Tyr Ser 
            20                  25                  30          


Ile Gly Leu Asp Ile Gly Thr Asn Ser Val Gly Trp Ala Val Ile Thr 
        35                  40                  45              


Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe Lys Val Leu Gly Asn Thr 
    50                  55                  60                  


Asp Arg His Ser Ile Lys Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp 
65                  70                  75                  80  


Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu Lys Arg Thr Ala Arg Arg 
                85                  90                  95      


Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe 
            100                 105                 110         


Ser Asn Glu Met Ala Lys Val Asp Asp Ser Phe Phe His Arg Leu Glu 
        115                 120                 125             


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


Phe Gly Asn Ile Val Asp Glu Val Ala Tyr His Glu Lys Tyr Pro Thr 
145                 150                 155                 160 


Ile Tyr His Leu Arg Lys Lys Leu Val Asp Ser Thr Asp Lys Ala Asp 
                165                 170                 175     


Leu Arg Leu Ile Tyr Leu Ala Leu Ala His Met Ile Lys Phe Arg Gly 
            180                 185                 190         


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


Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu 
    210                 215                 220                 


Asn Pro Ile Asn Ala Ser Gly Val Asp Ala Lys Ala Ile Leu Ser Ala 
225                 230                 235                 240 


Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro 
                245                 250                 255     


Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu 
            260                 265                 270         


Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe Asp Leu Ala Glu Asp Ala 
        275                 280                 285             


Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu 
    290                 295                 300                 


Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys 
305                 310                 315                 320 


Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp Ile Leu Arg Val Asn Thr 
                325                 330                 335     


Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp 
            340                 345                 350         


Glu His His Gln Asp Leu Thr Leu Leu Lys Ala Leu Val Arg Gln Gln 
        355                 360                 365             


Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe Asp Gln Ser Lys Asn Gly 
    370                 375                 380                 


Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys 
385                 390                 395                 400 


Phe Ile Lys Pro Ile Leu Glu Lys Met Asp Gly Thr Glu Glu Leu Leu 
                405                 410                 415     


Val Lys Leu Asn Arg Glu Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp 
            420                 425                 430         


Asn Gly Ser Ile Pro His Gln Ile His Leu Gly Glu Leu His Ala Ile 
        435                 440                 445             


Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu 
    450                 455                 460                 


Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro 
465                 470                 475                 480 


Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp Met Thr Arg Lys Ser Glu 
                485                 490                 495     


Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu Val Val Asp Lys Gly Ala 
            500                 505                 510         


Ser Ala Gln Ser Phe Ile Glu Arg Met Thr Asn Phe Asp Lys Asn Leu 
        515                 520                 525             


Pro Asn Glu Lys Val Leu Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe 
    530                 535                 540                 


Thr Val Tyr Asn Glu Leu Thr Lys Val Lys Tyr Val Thr Glu Gly Met 
545                 550                 555                 560 


Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln Lys Lys Ala Ile Val Asp 
                565                 570                 575     


Leu Leu Phe Lys Thr Asn Arg Lys Val Thr Val Lys Gln Leu Lys Glu 
            580                 585                 590         


Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp Ser Val Glu Ile Ser Gly 
        595                 600                 605             


Val Glu Asp Arg Phe Asn Ala Ser Leu Gly Thr Tyr His Asp Leu Leu 
    610                 615                 620                 


Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp 
625                 630                 635                 640 


Ile Leu Glu Asp Ile Val Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu 
                645                 650                 655     


Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala His Leu Phe Asp Asp Lys 
            660                 665                 670         


Val Met Lys Gln Leu Lys Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu 
        675                 680                 685             


Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr 
    690                 695                 700                 


Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe Ala Asn Arg Asn Phe Met 
705                 710                 715                 720 


Gln Leu Ile His Asp Asp Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys 
                725                 730                 735     


Ala Gln Val Ser Gly Gln Gly Asp Ser Leu His Glu His Ile Ala Asn 
            740                 745                 750         


Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val Lys 
        755                 760                 765             


Val Val Asp Glu Leu Val Lys Val Met Gly Arg His Lys Pro Glu Asn 
    770                 775                 780                 


Ile Val Ile Glu Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln 
785                 790                 795                 800 


Lys Asn Ser Arg Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys Glu 
                805                 810                 815     


Leu Gly Ser Gln Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln Leu 
            820                 825                 830         


Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met 
        835                 840                 845             


Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val 
    850                 855                 860                 


Asp His Ile Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn 
865                 870                 875                 880 


Lys Val Leu Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn Val 
                885                 890                 895     


Pro Ser Glu Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg Gln Leu 
            900                 905                 910         


Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn Leu Thr Lys 
        915                 920                 925             


Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys Ala Gly Phe Ile Lys 
    930                 935                 940                 


Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Gln Ile 
945                 950                 955                 960 


Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp Glu Asn Asp Lys Leu Ile 
                965                 970                 975     


Arg Glu Val Lys Val Ile Thr Leu Lys Ser Lys Leu Val Ser Asp Phe 
            980                 985                 990         


Arg Lys Asp Phe Gln Phe Tyr Lys  Val Arg Glu Ile Asn  Asn Tyr His 
        995                 1000                 1005             


His Ala  His Asp Ala Tyr Leu  Asn Ala Val Val Gly  Thr Ala Leu 
    1010                 1015                 1020             


Ile Lys  Lys Tyr Pro Lys Leu  Glu Ser Glu Phe Val  Tyr Gly Asp 
    1025                 1030                 1035             


Tyr Lys  Val Tyr Asp Val Arg  Lys Met Ile Ala Lys  Ser Glu Gln 
    1040                 1045                 1050             


Glu Ile  Gly Lys Ala Thr Ala  Lys Tyr Phe Phe Tyr  Ser Asn Ile 
    1055                 1060                 1065             


Met Asn  Phe Phe Lys Thr Glu  Ile Thr Leu Ala Asn  Gly Glu Ile 
    1070                 1075                 1080             


Arg Lys  Arg Pro Leu Ile Glu  Thr Asn Gly Glu Thr  Gly Glu Ile 
    1085                 1090                 1095             


Val Trp  Asp Lys Gly Arg Asp  Phe Ala Thr Val Arg  Lys Val Leu 
    1100                 1105                 1110             


Ser Met  Pro Gln Val Asn Ile  Val Lys Lys Thr Glu  Val Gln Thr 
    1115                 1120                 1125             


Gly Gly  Phe Ser Lys Glu Ser  Ile Leu Pro Lys Arg  Asn Ser Asp 
    1130                 1135                 1140             


Lys Leu  Ile Ala Arg Lys Lys  Asp Trp Asp Pro Lys  Lys Tyr Gly 
    1145                 1150                 1155             


Gly Phe  Asp Ser Pro Thr Val  Ala Tyr Ser Val Leu  Val Val Ala 
    1160                 1165                 1170             


Lys Val  Glu Lys Gly Lys Ser  Lys Lys Leu Lys Ser  Val Lys Glu 
    1175                 1180                 1185             


Leu Leu  Gly Ile Thr Ile Met  Glu Arg Ser Ser Phe  Glu Lys Asn 
    1190                 1195                 1200             


Pro Ile  Asp Phe Leu Glu Ala  Lys Gly Tyr Lys Glu  Val Lys Lys 
    1205                 1210                 1215             


Asp Leu  Ile Ile Lys Leu Pro  Lys Tyr Ser Leu Phe  Glu Leu Glu 
    1220                 1225                 1230             


Asn Gly  Arg Lys Arg Met Leu  Ala Ser Ala Gly Glu  Leu Gln Lys 
    1235                 1240                 1245             


Gly Asn  Glu Leu Ala Leu Pro  Ser Lys Tyr Val Asn  Phe Leu Tyr 
    1250                 1255                 1260             


Leu Ala  Ser His Tyr Glu Lys  Leu Lys Gly Ser Pro  Glu Asp Asn 
    1265                 1270                 1275             


Glu Gln  Lys Gln Leu Phe Val  Glu Gln His Lys His  Tyr Leu Asp 
    1280                 1285                 1290             


Glu Ile  Ile Glu Gln Ile Ser  Glu Phe Ser Lys Arg  Val Ile Leu 
    1295                 1300                 1305             


Ala Asp  Ala Asn Leu Asp Lys  Val Leu Ser Ala Tyr  Asn Lys His 
    1310                 1315                 1320             


Arg Asp  Lys Pro Ile Arg Glu  Gln Ala Glu Asn Ile  Ile His Leu 
    1325                 1330                 1335             


Phe Thr  Leu Thr Asn Leu Gly  Ala Pro Ala Ala Phe  Lys Tyr Phe 
    1340                 1345                 1350             


Asp Thr  Thr Ile Asp Arg Lys  Arg Tyr Thr Ser Thr  Lys Glu Val 
    1355                 1360                 1365             


Leu Asp  Ala Thr Leu Ile His  Gln Ser Ile Thr Gly  Leu Tyr Glu 
    1370                 1375                 1380             


Thr Arg  Ile Asp Leu Ser Gln  Leu Gly Gly Asp Gly  Ser Ala Ala 
    1385                 1390                 1395             


Pro Lys  Lys Lys Arg Lys Val  Asp 
    1400                 1405     


<210>  14
<211>  1404
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  SMF-Cas9-S

<400>  14

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


Ser Glu Glu Asp Leu Gly Gly Ser Gly Asp Lys Lys Tyr Ser Ile Gly 
            20                  25                  30          


Leu Asp Ile Gly Thr Asn Ser Val Gly Trp Ala Val Ile Thr Asp Glu 
        35                  40                  45              


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


His Ser Ile Lys Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp Ser Gly 
65                  70                  75                  80  


Glu Thr Ala Glu Ala Thr Arg Leu Lys Arg Thr Ala Arg Arg Arg Tyr 
                85                  90                  95      


Thr Arg Arg Lys Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe Ser Asn 
            100                 105                 110         


Glu Met Ala Lys Val Asp Asp Ser Phe Phe His Arg Leu Glu Glu Ser 
        115                 120                 125             


Phe Leu Val Glu Glu Asp Lys Lys His Glu Arg His Pro Ile Phe Gly 
    130                 135                 140                 


Asn Ile Val Asp Glu Val Ala Tyr His Glu Lys Tyr Pro Thr Ile Tyr 
145                 150                 155                 160 


His Leu Arg Lys Lys Leu Val Asp Ser Thr Asp Lys Ala Asp Leu Arg 
                165                 170                 175     


Leu Ile Tyr Leu Ala Leu Ala His Met Ile Lys Phe Arg Gly His Phe 
            180                 185                 190         


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


Phe Ile Gln Leu Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu Asn Pro 
    210                 215                 220                 


Ile Asn Ala Ser Gly Val Asp Ala Lys Ala Ile Leu Ser Ala Arg Leu 
225                 230                 235                 240 


Ser Lys Ser Arg Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro Gly Glu 
                245                 250                 255     


Lys Lys Asn Gly Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu Gly Leu 
            260                 265                 270         


Thr Pro Asn Phe Lys Ser Asn Phe Asp Leu Ala Glu Asp Ala Lys Leu 
        275                 280                 285             


Gln Leu Ser Lys Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu Leu Ala 
    290                 295                 300                 


Gln Ile Gly Asp Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys Asn Leu 
305                 310                 315                 320 


Ser Asp Ala Ile Leu Leu Ser Asp Ile Leu Arg Val Asn Thr Glu Ile 
                325                 330                 335     


Thr Lys Ala Pro Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp Glu His 
            340                 345                 350         


His Gln Asp Leu Thr Leu Leu Lys Ala Leu Val Arg Gln Gln Leu Pro 
        355                 360                 365             


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


Gly Tyr Ile Asp Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys Phe Ile 
385                 390                 395                 400 


Lys Pro Ile Leu Glu Lys Met Asp Gly Thr Glu Glu Leu Leu Val Lys 
                405                 410                 415     


Leu Asn Arg Glu Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp Asn Gly 
            420                 425                 430         


Ser Ile Pro His Gln Ile His Leu Gly Glu Leu His Ala Ile Leu Arg 
        435                 440                 445             


Arg Gln Glu Asp Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu Lys Ile 
    450                 455                 460                 


Glu Lys Ile Leu Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro Leu Ala 
465                 470                 475                 480 


Arg Gly Asn Ser Arg Phe Ala Trp Met Thr Arg Lys Ser Glu Glu Thr 
                485                 490                 495     


Ile Thr Pro Trp Asn Phe Glu Glu Val Val Asp Lys Gly Ala Ser Ala 
            500                 505                 510         


Gln Ser Phe Ile Glu Arg Met Thr Asn Phe Asp Lys Asn Leu Pro Asn 
        515                 520                 525             


Glu Lys Val Leu Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe Thr Val 
    530                 535                 540                 


Tyr Asn Glu Leu Thr Lys Val Lys Tyr Val Thr Glu Gly Met Arg Lys 
545                 550                 555                 560 


Pro Ala Phe Leu Ser Gly Glu Gln Lys Lys Ala Ile Val Asp Leu Leu 
                565                 570                 575     


Phe Lys Thr Asn Arg Lys Val Thr Val Lys Gln Leu Lys Glu Asp Tyr 
            580                 585                 590         


Phe Lys Lys Ile Glu Cys Phe Asp Ser Val Glu Ile Ser Gly Val Glu 
        595                 600                 605             


Asp Arg Phe Asn Ala Ser Leu Gly Thr Tyr His Asp Leu Leu Lys Ile 
    610                 615                 620                 


Ile Lys Asp Lys Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile Leu 
625                 630                 635                 640 


Glu Asp Ile Val Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu Met Ile 
                645                 650                 655     


Glu Glu Arg Leu Lys Thr Tyr Ala His Leu Phe Asp Asp Lys Val Met 
            660                 665                 670         


Lys Gln Leu Lys Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser Arg 
        675                 680                 685             


Lys Leu Ile Asn Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile Leu 
    690                 695                 700                 


Asp Phe Leu Lys Ser Asp Gly Phe Ala Asn Arg Asn Phe Met Gln Leu 
705                 710                 715                 720 


Ile His Asp Asp Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala Gln 
                725                 730                 735     


Val Ser Gly Gln Gly Asp Ser Leu His Glu His Ile Ala Asn Leu Ala 
            740                 745                 750         


Gly Ser Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val 
        755                 760                 765             


Asp Glu Leu Val Lys Val Met Gly Arg His Lys Pro Glu Asn Ile Val 
    770                 775                 780                 


Ile Glu Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn 
785                 790                 795                 800 


Ser Arg Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly 
                805                 810                 815     


Ser Gln Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn 
            820                 825                 830         


Glu Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val 
        835                 840                 845             


Asp Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp His 
    850                 855                 860                 


Ile Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn Lys Val 
865                 870                 875                 880 


Leu Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn Val Pro Ser 
                885                 890                 895     


Glu Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg Gln Leu Leu Asn 
            900                 905                 910         


Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn Leu Thr Lys Ala Glu 
        915                 920                 925             


Arg Gly Gly Leu Ser Glu Leu Asp Lys Ala Gly Phe Ile Lys Arg Gln 
    930                 935                 940                 


Leu Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Gln Ile Leu Asp 
945                 950                 955                 960 


Ser Arg Met Asn Thr Lys Tyr Asp Glu Asn Asp Lys Leu Ile Arg Glu 
                965                 970                 975     


Val Lys Val Ile Thr Leu Lys Ser Lys Leu Val Ser Asp Phe Arg Lys 
            980                 985                 990         


Asp Phe Gln Phe Tyr Lys Val Arg  Glu Ile Asn Asn Tyr  His His Ala 
        995                 1000                 1005             


His Asp  Ala Tyr Leu Asn Ala  Val Val Gly Thr Ala  Leu Ile Lys 
    1010                 1015                 1020             


Lys Tyr  Pro Lys Leu Glu Ser  Glu Phe Val Tyr Gly  Asp Tyr Lys 
    1025                 1030                 1035             


Val Tyr  Asp Val Arg Lys Met  Ile Ala Lys Ser Glu  Gln Glu Ile 
    1040                 1045                 1050             


Gly Lys  Ala Thr Ala Lys Tyr  Phe Phe Tyr Ser Asn  Ile Met Asn 
    1055                 1060                 1065             


Phe Phe  Lys Thr Glu Ile Thr  Leu Ala Asn Gly Glu  Ile Arg Lys 
    1070                 1075                 1080             


Arg Pro  Leu Ile Glu Thr Asn  Gly Glu Thr Gly Glu  Ile Val Trp 
    1085                 1090                 1095             


Asp Lys  Gly Arg Asp Phe Ala  Thr Val Arg Lys Val  Leu Ser Met 
    1100                 1105                 1110             


Pro Gln  Val Asn Ile Val Lys  Lys Thr Glu Val Gln  Thr Gly Gly 
    1115                 1120                 1125             


Phe Ser  Lys Glu Ser Ile Leu  Pro Lys Arg Asn Ser  Asp Lys Leu 
    1130                 1135                 1140             


Ile Ala  Arg Lys Lys Asp Trp  Asp Pro Lys Lys Tyr  Gly Gly Phe 
    1145                 1150                 1155             


Asp Ser  Pro Thr Val Ala Tyr  Ser Val Leu Val Val  Ala Lys Val 
    1160                 1165                 1170             


Glu Lys  Gly Lys Ser Lys Lys  Leu Lys Ser Val Lys  Glu Leu Leu 
    1175                 1180                 1185             


Gly Ile  Thr Ile Met Glu Arg  Ser Ser Phe Glu Lys  Asn Pro Ile 
    1190                 1195                 1200             


Asp Phe  Leu Glu Ala Lys Gly  Tyr Lys Glu Val Lys  Lys Asp Leu 
    1205                 1210                 1215             


Ile Ile  Lys Leu Pro Lys Tyr  Ser Leu Phe Glu Leu  Glu Asn Gly 
    1220                 1225                 1230             


Arg Lys  Arg Met Leu Ala Ser  Ala Gly Glu Leu Gln  Lys Gly Asn 
    1235                 1240                 1245             


Glu Leu  Ala Leu Pro Ser Lys  Tyr Val Asn Phe Leu  Tyr Leu Ala 
    1250                 1255                 1260             


Ser His  Tyr Glu Lys Leu Lys  Gly Ser Pro Glu Asp  Asn Glu Gln 
    1265                 1270                 1275             


Lys Gln  Leu Phe Val Glu Gln  His Lys His Tyr Leu  Asp Glu Ile 
    1280                 1285                 1290             


Ile Glu  Gln Ile Ser Glu Phe  Ser Lys Arg Val Ile  Leu Ala Asp 
    1295                 1300                 1305             


Ala Asn  Leu Asp Lys Val Leu  Ser Ala Tyr Asn Lys  His Arg Asp 
    1310                 1315                 1320             


Lys Pro  Ile Arg Glu Gln Ala  Glu Asn Ile Ile His  Leu Phe Thr 
    1325                 1330                 1335             


Leu Thr  Asn Leu Gly Ala Pro  Ala Ala Phe Lys Tyr  Phe Asp Thr 
    1340                 1345                 1350             


Thr Ile  Asp Arg Lys Arg Tyr  Thr Ser Thr Lys Glu  Val Leu Asp 
    1355                 1360                 1365             


Ala Thr  Leu Ile His Gln Ser  Ile Thr Gly Leu Tyr  Glu Thr Arg 
    1370                 1375                 1380             


Ile Asp  Leu Ser Gln Leu Gly  Gly Asp Gly Ser Ala  Ala Pro Lys 
    1385                 1390                 1395             


Lys Lys  Arg Lys Val Asp 
    1400                 


<210>  15
<211>  1404
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  OMF-Cas9-O

<400>  15

Met Pro Pro Pro Lys Arg Pro Arg Leu Asp Leu Glu Glu Gln Lys Leu 
1               5                   10                  15      


Ile Ser Glu Glu Asp Leu Gly Gly Ser Gly Asp Lys Lys Tyr Ser Ile 
            20                  25                  30          


Gly Leu Asp Ile Gly Thr Asn Ser Val Gly Trp Ala Val Ile Thr Asp 
        35                  40                  45              


Glu Tyr Lys Val Pro Ser Lys Lys Phe Lys Val Leu Gly Asn Thr Asp 
    50                  55                  60                  


Arg His Ser Ile Lys Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp Ser 
65                  70                  75                  80  


Gly Glu Thr Ala Glu Ala Thr Arg Leu Lys Arg Thr Ala Arg Arg Arg 
                85                  90                  95      


Tyr Thr Arg Arg Lys Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe Ser 
            100                 105                 110         


Asn Glu Met Ala Lys Val Asp Asp Ser Phe Phe His Arg Leu Glu Glu 
        115                 120                 125             


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


Gly Asn Ile Val Asp Glu Val Ala Tyr His Glu Lys Tyr Pro Thr Ile 
145                 150                 155                 160 


Tyr His Leu Arg Lys Lys Leu Val Asp Ser Thr Asp Lys Ala Asp Leu 
                165                 170                 175     


Arg Leu Ile Tyr Leu Ala Leu Ala His Met Ile Lys Phe Arg Gly His 
            180                 185                 190         


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


Leu Phe Ile Gln Leu Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu Asn 
    210                 215                 220                 


Pro Ile Asn Ala Ser Gly Val Asp Ala Lys Ala Ile Leu Ser Ala Arg 
225                 230                 235                 240 


Leu Ser Lys Ser Arg Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro Gly 
                245                 250                 255     


Glu Lys Lys Asn Gly Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu Gly 
            260                 265                 270         


Leu Thr Pro Asn Phe Lys Ser Asn Phe Asp Leu Ala Glu Asp Ala Lys 
        275                 280                 285             


Leu Gln Leu Ser Lys Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu Leu 
    290                 295                 300                 


Ala Gln Ile Gly Asp Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys Asn 
305                 310                 315                 320 


Leu Ser Asp Ala Ile Leu Leu Ser Asp Ile Leu Arg Val Asn Thr Glu 
                325                 330                 335     


Ile Thr Lys Ala Pro Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp Glu 
            340                 345                 350         


His His Gln Asp Leu Thr Leu Leu Lys Ala Leu Val Arg Gln Gln Leu 
        355                 360                 365             


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


Ala Gly Tyr Ile Asp Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys Phe 
385                 390                 395                 400 


Ile Lys Pro Ile Leu Glu Lys Met Asp Gly Thr Glu Glu Leu Leu Val 
                405                 410                 415     


Lys Leu Asn Arg Glu Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp Asn 
            420                 425                 430         


Gly Ser Ile Pro His Gln Ile His Leu Gly Glu Leu His Ala Ile Leu 
        435                 440                 445             


Arg Arg Gln Glu Asp Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu Lys 
    450                 455                 460                 


Ile Glu Lys Ile Leu Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro Leu 
465                 470                 475                 480 


Ala Arg Gly Asn Ser Arg Phe Ala Trp Met Thr Arg Lys Ser Glu Glu 
                485                 490                 495     


Thr Ile Thr Pro Trp Asn Phe Glu Glu Val Val Asp Lys Gly Ala Ser 
            500                 505                 510         


Ala Gln Ser Phe Ile Glu Arg Met Thr Asn Phe Asp Lys Asn Leu Pro 
        515                 520                 525             


Asn Glu Lys Val Leu Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe Thr 
    530                 535                 540                 


Val Tyr Asn Glu Leu Thr Lys Val Lys Tyr Val Thr Glu Gly Met Arg 
545                 550                 555                 560 


Lys Pro Ala Phe Leu Ser Gly Glu Gln Lys Lys Ala Ile Val Asp Leu 
                565                 570                 575     


Leu Phe Lys Thr Asn Arg Lys Val Thr Val Lys Gln Leu Lys Glu Asp 
            580                 585                 590         


Tyr Phe Lys Lys Ile Glu Cys Phe Asp Ser Val Glu Ile Ser Gly Val 
        595                 600                 605             


Glu Asp Arg Phe Asn Ala Ser Leu Gly Thr Tyr His Asp Leu Leu Lys 
    610                 615                 620                 


Ile Ile Lys Asp Lys Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile 
625                 630                 635                 640 


Leu Glu Asp Ile Val Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu Met 
                645                 650                 655     


Ile Glu Glu Arg Leu Lys Thr Tyr Ala His Leu Phe Asp Asp Lys Val 
            660                 665                 670         


Met Lys Gln Leu Lys Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser 
        675                 680                 685             


Arg Lys Leu Ile Asn Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile 
    690                 695                 700                 


Leu Asp Phe Leu Lys Ser Asp Gly Phe Ala Asn Arg Asn Phe Met Gln 
705                 710                 715                 720 


Leu Ile His Asp Asp Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala 
                725                 730                 735     


Gln Val Ser Gly Gln Gly Asp Ser Leu His Glu His Ile Ala Asn Leu 
            740                 745                 750         


Ala Gly Ser Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val 
        755                 760                 765             


Val Asp Glu Leu Val Lys Val Met Gly Arg His Lys Pro Glu Asn Ile 
    770                 775                 780                 


Val Ile Glu Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys 
785                 790                 795                 800 


Asn Ser Arg Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu 
                805                 810                 815     


Gly Ser Gln Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln 
            820                 825                 830         


Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr 
        835                 840                 845             


Val Asp Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp 
    850                 855                 860                 


His Ile Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn Lys 
865                 870                 875                 880 


Val Leu Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn Val Pro 
                885                 890                 895     


Ser Glu Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg Gln Leu Leu 
            900                 905                 910         


Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn Leu Thr Lys Ala 
        915                 920                 925             


Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys Ala Gly Phe Ile Lys Arg 
    930                 935                 940                 


Gln Leu Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Gln Ile Leu 
945                 950                 955                 960 


Asp Ser Arg Met Asn Thr Lys Tyr Asp Glu Asn Asp Lys Leu Ile Arg 
                965                 970                 975     


Glu Val Lys Val Ile Thr Leu Lys Ser Lys Leu Val Ser Asp Phe Arg 
            980                 985                 990         


Lys Asp Phe Gln Phe Tyr Lys Val  Arg Glu Ile Asn Asn  Tyr His His 
        995                 1000                 1005             


Ala His  Asp Ala Tyr Leu Asn  Ala Val Val Gly Thr  Ala Leu Ile 
    1010                 1015                 1020             


Lys Lys  Tyr Pro Lys Leu Glu  Ser Glu Phe Val Tyr  Gly Asp Tyr 
    1025                 1030                 1035             


Lys Val  Tyr Asp Val Arg Lys  Met Ile Ala Lys Ser  Glu Gln Glu 
    1040                 1045                 1050             


Ile Gly  Lys Ala Thr Ala Lys  Tyr Phe Phe Tyr Ser  Asn Ile Met 
    1055                 1060                 1065             


Asn Phe  Phe Lys Thr Glu Ile  Thr Leu Ala Asn Gly  Glu Ile Arg 
    1070                 1075                 1080             


Lys Arg  Pro Leu Ile Glu Thr  Asn Gly Glu Thr Gly  Glu Ile Val 
    1085                 1090                 1095             


Trp Asp  Lys Gly Arg Asp Phe  Ala Thr Val Arg Lys  Val Leu Ser 
    1100                 1105                 1110             


Met Pro  Gln Val Asn Ile Val  Lys Lys Thr Glu Val  Gln Thr Gly 
    1115                 1120                 1125             


Gly Phe  Ser Lys Glu Ser Ile  Leu Pro Lys Arg Asn  Ser Asp Lys 
    1130                 1135                 1140             


Leu Ile  Ala Arg Lys Lys Asp  Trp Asp Pro Lys Lys  Tyr Gly Gly 
    1145                 1150                 1155             


Phe Asp  Ser Pro Thr Val Ala  Tyr Ser Val Leu Val  Val Ala Lys 
    1160                 1165                 1170             


Val Glu  Lys Gly Lys Ser Lys  Lys Leu Lys Ser Val  Lys Glu Leu 
    1175                 1180                 1185             


Leu Gly  Ile Thr Ile Met Glu  Arg Ser Ser Phe Glu  Lys Asn Pro 
    1190                 1195                 1200             


Ile Asp  Phe Leu Glu Ala Lys  Gly Tyr Lys Glu Val  Lys Lys Asp 
    1205                 1210                 1215             


Leu Ile  Ile Lys Leu Pro Lys  Tyr Ser Leu Phe Glu  Leu Glu Asn 
    1220                 1225                 1230             


Gly Arg  Lys Arg Met Leu Ala  Ser Ala Gly Glu Leu  Gln Lys Gly 
    1235                 1240                 1245             


Asn Glu  Leu Ala Leu Pro Ser  Lys Tyr Val Asn Phe  Leu Tyr Leu 
    1250                 1255                 1260             


Ala Ser  His Tyr Glu Lys Leu  Lys Gly Ser Pro Glu  Asp Asn Glu 
    1265                 1270                 1275             


Gln Lys  Gln Leu Phe Val Glu  Gln His Lys His Tyr  Leu Asp Glu 
    1280                 1285                 1290             


Ile Ile  Glu Gln Ile Ser Glu  Phe Ser Lys Arg Val  Ile Leu Ala 
    1295                 1300                 1305             


Asp Ala  Asn Leu Asp Lys Val  Leu Ser Ala Tyr Asn  Lys His Arg 
    1310                 1315                 1320             


Asp Lys  Pro Ile Arg Glu Gln  Ala Glu Asn Ile Ile  His Leu Phe 
    1325                 1330                 1335             


Thr Leu  Thr Asn Leu Gly Ala  Pro Ala Ala Phe Lys  Tyr Phe Asp 
    1340                 1345                 1350             


Thr Thr  Ile Asp Arg Lys Arg  Tyr Thr Ser Thr Lys  Glu Val Leu 
    1355                 1360                 1365             


Asp Ala  Thr Leu Ile His Gln  Ser Ile Thr Gly Leu  Tyr Glu Thr 
    1370                 1375                 1380             


Arg Ile  Asp Leu Ser Gln Leu  Gly Gly Asp Gly Ser  Pro Pro Pro 
    1385                 1390                 1395             


Lys Arg  Pro Arg Leu Asp 
    1400                 


<210>  16
<211>  4215
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HeiCas9 encoding sequence

<400>  16
atggagcaga agctgatcag cgaggaggac ctgggaggaa gcggaccacc tcccaagagg       60

cccaggctgg acctcgagga taaaaagtat tctattggtt tagacatcgg caccaacagc      120

gtgggctggg ccgtgatcac cgacgagtac aaggtgccca gcaagaaatt caaggtgctg      180

ggcaacaccg acagacacag catcaagaaa aacctgatcg gcgccctgct cttcgactcc      240

ggcgaaaccg ccgaggccac cagactgaag agaaccgcca gacggagata caccagacgg      300

aagaatagaa tctgctacct gcaggagatc ttcagcaacg agatggccaa ggtggacgat      360

agcttctttc acagactgga agagagcttc ctggtggaag aggacaagaa acacgagaga      420

caccccatct tcggcaacat cgtggacgag gtggcctacc acgagaagta ccccaccatc      480

taccacctga gaaagaaact ggtggacagc accgacaagg ccgacctgag actgatctac      540

ctggcactgg cccacatgat caagttcaga ggccacttcc tgatcgaggg cgacctgaac      600

cccgacaaca gcgacgtgga caagctgttc atccagctgg tgcagaccta caaccagctg      660

ttcgaagaga accctatcaa cgccagcggc gtggacgcca aggccatcct gagcgccaga      720

ctcagcaaga gcagacggct ggagaacctg atcgcccagc tgcccggcga gaagaaaaac      780

ggcctgttcg gcaacctgat cgccctgagc ctgggcctga cccccaactt caagagcaac      840

ttcgacctgg ccgaggacgc caagctgcag ctgagcaagg acacctacga cgatgacctg      900

gacaacctcc tggcccagat cggcgaccag tacgccgacc tgttcctcgc agccaagaac      960

ctgagcgacg ccatcctcct gagcgacatc ctcagagtga acaccgagat caccaaggct     1020

cccctgagcg ccagcatgat caagagatac gacgagcacc atcaggacct gaccctcctg     1080

aaggccctcg tgagacaaca gctgcccgag aagtacaagg agatcttctt tgaccagagc     1140

aagaacggct acgccggcta catcgacgga ggcgccagtc aggaagagtt ctacaagttc     1200

atcaagccca tcctggagaa gatggacggc accgaagagc tgctcgtgaa gctgaacaga     1260

gaggacctgc tcagaaagca gagaaccttc gacaacggca gcatccccca ccagatccac     1320

ctgggcgagc tgcacgccat cctgagacgg caggaggact tctacccctt cctgaaggac     1380

aacagagaga agattgaaaa gatcctgacc ttcagaatcc cctactatgt gggccccctg     1440

gccagaggca acagcagatt cgcctggatg accaggaaga gcgaagagac aatcacacct     1500

tggaacttcg aagaggtggt cgacaaaggc gccagcgccc agagcttcat cgagagaatg     1560

accaacttcg acaagaacct gcccaacgag aaggtgctgc ccaagcacag cctcctgtac     1620

gagtacttca ccgtgtacaa cgagctgacc aaggtgaagt acgtgaccga gggcatgaga     1680

aagcctgcct ttctgagtgg cgagcagaag aaagccatcg tggacctgct cttcaagacc     1740

aacagaaaag tgaccgtgaa gcagctgaag gaggactact tcaagaaaat cgagtgcttc     1800

gacagcgtgg agatcagcgg cgtggaggac agattcaacg ccagcctggg cacctaccac     1860

gacctgctca agattatcaa agacaaggac ttcctggaca acgaagagaa cgaggacatc     1920

ctggaggaca tcgtgctgac actgaccctc ttcgaggaca gagagatgat cgaagagaga     1980

ctgaagacct acgcccacct gttcgatgac aaggtgatga agcagctgaa gagacggaga     2040

tacaccggct ggggcagact gagcagaaag ctgatcaacg gcatcagaga caagcagagc     2100

ggcaagacca tcctggactt cctgaagagc gacggcttcg ccaacagaaa cttcatgcag     2160

ctgatccacg atgacagcct gaccttcaag gaggacatcc agaaagccca agtgagcggg     2220

cagggcgaca gcctgcacga gcatatcgcc aacctggctg gcagccccgc catcaagaaa     2280

ggcatcctgc agaccgtgaa ggtcgtggac gagctggtca aggtgatggg cagacacaag     2340

cccgagaaca tcgtgattga gatggccaga gagaaccaga caacccagaa gggccagaag     2400

aacagcagag agagaatgaa gagaatcgaa gagggcatca aggagctggg cagccagatc     2460

ctgaaggagc accccgtgga gaacacccag ctgcagaacg agaagctgta cctgtattac     2520

ctgcagaacg gcagagacat gtacgtggac caggagctgg acatcaacag actgagcgat     2580

tacgacgtgg atcacatcgt cccccagagc ttcctgaagg atgacagcat cgataacaag     2640

gtgctgacca gaagcgacaa gaacagaggc aagagcgaca acgtgcccag cgaagaggtc     2700

gtgaagaaaa tgaagaacta ctggagacag ctcctgaacg ccaagctgat cacccagaga     2760

aagttcgaca acctgaccaa ggccgagaga ggcgggctga gcgagctcga caaagccggc     2820

ttcatcaaga gacagctggt ggaaaccaga cagatcacca agcacgtggc ccagatcctg     2880

gacagcagaa tgaacaccaa gtacgacgag aacgataagc tgatcagaga ggtgaaggtc     2940

atcaccctga agagcaaact ggtgagcgac ttcagaaagg acttccagtt ctacaaggtg     3000

agagagatca ataactacca tcacgctcat gacgcctacc tgaacgccgt cgtgggcacc     3060

gccctgatca agaaataccc caagctggag agcgagttcg tgtacggcga ctacaaggtg     3120

tacgacgtga gaaagatgat cgccaagagc gagcaggaga tcggcaaggc caccgccaag     3180

tacttctttt acagcaacat catgaacttc tttaagaccg agatcaccct ggccaacggc     3240

gagatcagaa agaggcccct gatcgaaacc aacggcgaaa ccggcgagat cgtgtgggac     3300

aagggcagag acttcgccac cgtgagaaag gtgctgagca tgccccaggt gaacatcgtg     3360

aagaaaaccg aggtgcagac cggaggcttc agcaaggaga gcatcctgcc caagagaaac     3420

agcgacaagc tgatcgccag aaagaaagac tgggacccca agaaatacgg aggcttcgac     3480

agccccaccg tggcctacag cgtgctggtc gtggccaagg tggagaaggg caagagcaag     3540

aaactgaaga gcgtgaagga gctcctgggc atcaccatca tggagagatc cagcttcgag     3600

aagaacccca tcgacttcct ggaggccaag ggctacaagg aggtgaagaa agacctgatt     3660

atcaagctgc ccaagtacag cctgttcgag ctggagaacg gcagaaagag aatgctggcc     3720

agcgccggcg agctgcagaa gggcaacgag ctggccctgc ccagcaagta cgtgaacttc     3780

ctgtacctgg ccagccacta cgagaagctg aagggcagcc ccgaggacaa cgagcagaag     3840

cagctgttcg tggagcagca caagcactac ctggacgaaa tcattgagca gatcagcgag     3900

ttcagtaaga gagtgatcct ggctgacgcc aacctggaca aggtgctgag cgcctacaac     3960

aagcacagag acaagcccat cagagagcag gccgagaaca tcattcacct gttcaccctg     4020

accaacctgg gcgcacccgc agccttcaag tacttcgaca ccacaatcga cagaaagaga     4080

tacaccagca ccaaggaggt gctggacgcc accctgatcc accagagcat caccggcctg     4140

tacgaaacca gaatcgacct gtcacagctt gggggtgacg gatcccctcc tcccaagagg     4200

cccaggctgg actaa                                                      4215


<210>  17
<211>  4221
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  MIS-Cas9-S encoding sequence

<400>  17
atggagcaga agctgatcag cgaggaggac ctgggtatcc acggagtccc agcagccgct       60

ccaaagaaga agcgtaaggt agataaaaag tattctattg gtttagacat cggcaccaac      120

agcgtgggct gggccgtgat caccgacgag tacaaggtgc ccagcaagaa attcaaggtg      180

ctgggcaaca ccgacagaca cagcatcaag aaaaacctga tcggcgccct gctcttcgac      240

tccggcgaaa ccgccgaggc caccagactg aagagaaccg ccagacggag atacaccaga      300

cggaagaata gaatctgcta cctgcaggag atcttcagca acgagatggc caaggtggac      360

gatagcttct ttcacagact ggaagagagc ttcctggtgg aagaggacaa gaaacacgag      420

agacacccca tcttcggcaa catcgtggac gaggtggcct accacgagaa gtaccccacc      480

atctaccacc tgagaaagaa actggtggac agcaccgaca aggccgacct gagactgatc      540

tacctggcac tggcccacat gatcaagttc agaggccact tcctgatcga gggcgacctg      600

aaccccgaca acagcgacgt ggacaagctg ttcatccagc tggtgcagac ctacaaccag      660

ctgttcgaag agaaccctat caacgccagc ggcgtggacg ccaaggccat cctgagcgcc      720

agactcagca agagcagacg gctggagaac ctgatcgccc agctgcccgg cgagaagaaa      780

aacggcctgt tcggcaacct gatcgccctg agcctgggcc tgacccccaa cttcaagagc      840

aacttcgacc tggccgagga cgccaagctg cagctgagca aggacaccta cgacgatgac      900

ctggacaacc tcctggccca gatcggcgac cagtacgccg acctgttcct cgcagccaag      960

aacctgagcg acgccatcct cctgagcgac atcctcagag tgaacaccga gatcaccaag     1020

gctcccctga gcgccagcat gatcaagaga tacgacgagc accatcagga cctgaccctc     1080

ctgaaggccc tcgtgagaca acagctgccc gagaagtaca aggagatctt ctttgaccag     1140

agcaagaacg gctacgccgg ctacatcgac ggaggcgcca gtcaggaaga gttctacaag     1200

ttcatcaagc ccatcctgga gaagatggac ggcaccgaag agctgctcgt gaagctgaac     1260

agagaggacc tgctcagaaa gcagagaacc ttcgacaacg gcagcatccc ccaccagatc     1320

cacctgggcg agctgcacgc catcctgaga cggcaggagg acttctaccc cttcctgaag     1380

gacaacagag agaagattga aaagatcctg accttcagaa tcccctacta tgtgggcccc     1440

ctggccagag gcaacagcag attcgcctgg atgaccagga agagcgaaga gacaatcaca     1500

ccttggaact tcgaagaggt ggtcgacaaa ggcgccagcg cccagagctt catcgagaga     1560

atgaccaact tcgacaagaa cctgcccaac gagaaggtgc tgcccaagca cagcctcctg     1620

tacgagtact tcaccgtgta caacgagctg accaaggtga agtacgtgac cgagggcatg     1680

agaaagcctg cctttctgag tggcgagcag aagaaagcca tcgtggacct gctcttcaag     1740

accaacagaa aagtgaccgt gaagcagctg aaggaggact acttcaagaa aatcgagtgc     1800

ttcgacagcg tggagatcag cggcgtggag gacagattca acgccagcct gggcacctac     1860

cacgacctgc tcaagattat caaagacaag gacttcctgg acaacgaaga gaacgaggac     1920

atcctggagg acatcgtgct gacactgacc ctcttcgagg acagagagat gatcgaagag     1980

agactgaaga cctacgccca cctgttcgat gacaaggtga tgaagcagct gaagagacgg     2040

agatacaccg gctggggcag actgagcaga aagctgatca acggcatcag agacaagcag     2100

agcggcaaga ccatcctgga cttcctgaag agcgacggct tcgccaacag aaacttcatg     2160

cagctgatcc acgatgacag cctgaccttc aaggaggaca tccagaaagc ccaagtgagc     2220

gggcagggcg acagcctgca cgagcatatc gccaacctgg ctggcagccc cgccatcaag     2280

aaaggcatcc tgcagaccgt gaaggtcgtg gacgagctgg tcaaggtgat gggcagacac     2340

aagcccgaga acatcgtgat tgagatggcc agagagaacc agacaaccca gaagggccag     2400

aagaacagca gagagagaat gaagagaatc gaagagggca tcaaggagct gggcagccag     2460

atcctgaagg agcaccccgt ggagaacacc cagctgcaga acgagaagct gtacctgtat     2520

tacctgcaga acggcagaga catgtacgtg gaccaggagc tggacatcaa cagactgagc     2580

gattacgacg tggatcacat cgtcccccag agcttcctga aggatgacag catcgataac     2640

aaggtgctga ccagaagcga caagaacaga ggcaagagcg acaacgtgcc cagcgaagag     2700

gtcgtgaaga aaatgaagaa ctactggaga cagctcctga acgccaagct gatcacccag     2760

agaaagttcg acaacctgac caaggccgag agaggcgggc tgagcgagct cgacaaagcc     2820

ggcttcatca agagacagct ggtggaaacc agacagatca ccaagcacgt ggcccagatc     2880

ctggacagca gaatgaacac caagtacgac gagaacgata agctgatcag agaggtgaag     2940

gtcatcaccc tgaagagcaa actggtgagc gacttcagaa aggacttcca gttctacaag     3000

gtgagagaga tcaataacta ccatcacgct catgacgcct acctgaacgc cgtcgtgggc     3060

accgccctga tcaagaaata ccccaagctg gagagcgagt tcgtgtacgg cgactacaag     3120

gtgtacgacg tgagaaagat gatcgccaag agcgagcagg agatcggcaa ggccaccgcc     3180

aagtacttct tttacagcaa catcatgaac ttctttaaga ccgagatcac cctggccaac     3240

ggcgagatca gaaagaggcc cctgatcgaa accaacggcg aaaccggcga gatcgtgtgg     3300

gacaagggca gagacttcgc caccgtgaga aaggtgctga gcatgcccca ggtgaacatc     3360

gtgaagaaaa ccgaggtgca gaccggaggc ttcagcaagg agagcatcct gcccaagaga     3420

aacagcgaca agctgatcgc cagaaagaaa gactgggacc ccaagaaata cggaggcttc     3480

gacagcccca ccgtggccta cagcgtgctg gtcgtggcca aggtggagaa gggcaagagc     3540

aagaaactga agagcgtgaa ggagctcctg ggcatcacca tcatggagag atccagcttc     3600

gagaagaacc ccatcgactt cctggaggcc aagggctaca aggaggtgaa gaaagacctg     3660

attatcaagc tgcccaagta cagcctgttc gagctggaga acggcagaaa gagaatgctg     3720

gccagcgccg gcgagctgca gaagggcaac gagctggccc tgcccagcaa gtacgtgaac     3780

ttcctgtacc tggccagcca ctacgagaag ctgaagggca gccccgagga caacgagcag     3840

aagcagctgt tcgtggagca gcacaagcac tacctggacg aaatcattga gcagatcagc     3900

gagttcagta agagagtgat cctggctgac gccaacctgg acaaggtgct gagcgcctac     3960

aacaagcaca gagacaagcc catcagagag caggccgaga acatcattca cctgttcacc     4020

ctgaccaacc tgggcgcacc cgcagccttc aagtacttcg acaccacaat cgacagaaag     4080

agatacacca gcaccaagga ggtgctggac gccaccctga tccaccagag catcaccggc     4140

ctgtacgaaa ccagaatcga cctgtcacag cttgggggtg acggatccgc tgctccaaag     4200

aagaagcgta aggtagatta a                                               4221


<210>  18
<211>  4215
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  SMF-Cas9-S encoding sequence

<400>  18
atggctccaa agaagaagcg taaggtactc gaggagcaga agctgatcag cgaggaggac       60

ctgggaggaa gcggagataa aaagtattct attggtttag acatcggcac caacagcgtg      120

ggctgggccg tgatcaccga cgagtacaag gtgcccagca agaaattcaa ggtgctgggc      180

aacaccgaca gacacagcat caagaaaaac ctgatcggcg ccctgctctt cgactccggc      240

gaaaccgccg aggccaccag actgaagaga accgccagac ggagatacac cagacggaag      300

aatagaatct gctacctgca ggagatcttc agcaacgaga tggccaaggt ggacgatagc      360

ttctttcaca gactggaaga gagcttcctg gtggaagagg acaagaaaca cgagagacac      420

cccatcttcg gcaacatcgt ggacgaggtg gcctaccacg agaagtaccc caccatctac      480

cacctgagaa agaaactggt ggacagcacc gacaaggccg acctgagact gatctacctg      540

gcactggccc acatgatcaa gttcagaggc cacttcctga tcgagggcga cctgaacccc      600

gacaacagcg acgtggacaa gctgttcatc cagctggtgc agacctacaa ccagctgttc      660

gaagagaacc ctatcaacgc cagcggcgtg gacgccaagg ccatcctgag cgccagactc      720

agcaagagca gacggctgga gaacctgatc gcccagctgc ccggcgagaa gaaaaacggc      780

ctgttcggca acctgatcgc cctgagcctg ggcctgaccc ccaacttcaa gagcaacttc      840

gacctggccg aggacgccaa gctgcagctg agcaaggaca cctacgacga tgacctggac      900

aacctcctgg cccagatcgg cgaccagtac gccgacctgt tcctcgcagc caagaacctg      960

agcgacgcca tcctcctgag cgacatcctc agagtgaaca ccgagatcac caaggctccc     1020

ctgagcgcca gcatgatcaa gagatacgac gagcaccatc aggacctgac cctcctgaag     1080

gccctcgtga gacaacagct gcccgagaag tacaaggaga tcttctttga ccagagcaag     1140

aacggctacg ccggctacat cgacggaggc gccagtcagg aagagttcta caagttcatc     1200

aagcccatcc tggagaagat ggacggcacc gaagagctgc tcgtgaagct gaacagagag     1260

gacctgctca gaaagcagag aaccttcgac aacggcagca tcccccacca gatccacctg     1320

ggcgagctgc acgccatcct gagacggcag gaggacttct accccttcct gaaggacaac     1380

agagagaaga ttgaaaagat cctgaccttc agaatcccct actatgtggg ccccctggcc     1440

agaggcaaca gcagattcgc ctggatgacc aggaagagcg aagagacaat cacaccttgg     1500

aacttcgaag aggtggtcga caaaggcgcc agcgcccaga gcttcatcga gagaatgacc     1560

aacttcgaca agaacctgcc caacgagaag gtgctgccca agcacagcct cctgtacgag     1620

tacttcaccg tgtacaacga gctgaccaag gtgaagtacg tgaccgaggg catgagaaag     1680

cctgcctttc tgagtggcga gcagaagaaa gccatcgtgg acctgctctt caagaccaac     1740

agaaaagtga ccgtgaagca gctgaaggag gactacttca agaaaatcga gtgcttcgac     1800

agcgtggaga tcagcggcgt ggaggacaga ttcaacgcca gcctgggcac ctaccacgac     1860

ctgctcaaga ttatcaaaga caaggacttc ctggacaacg aagagaacga ggacatcctg     1920

gaggacatcg tgctgacact gaccctcttc gaggacagag agatgatcga agagagactg     1980

aagacctacg cccacctgtt cgatgacaag gtgatgaagc agctgaagag acggagatac     2040

accggctggg gcagactgag cagaaagctg atcaacggca tcagagacaa gcagagcggc     2100

aagaccatcc tggacttcct gaagagcgac ggcttcgcca acagaaactt catgcagctg     2160

atccacgatg acagcctgac cttcaaggag gacatccaga aagcccaagt gagcgggcag     2220

ggcgacagcc tgcacgagca tatcgccaac ctggctggca gccccgccat caagaaaggc     2280

atcctgcaga ccgtgaaggt cgtggacgag ctggtcaagg tgatgggcag acacaagccc     2340

gagaacatcg tgattgagat ggccagagag aaccagacaa cccagaaggg ccagaagaac     2400

agcagagaga gaatgaagag aatcgaagag ggcatcaagg agctgggcag ccagatcctg     2460

aaggagcacc ccgtggagaa cacccagctg cagaacgaga agctgtacct gtattacctg     2520

cagaacggca gagacatgta cgtggaccag gagctggaca tcaacagact gagcgattac     2580

gacgtggatc acatcgtccc ccagagcttc ctgaaggatg acagcatcga taacaaggtg     2640

ctgaccagaa gcgacaagaa cagaggcaag agcgacaacg tgcccagcga agaggtcgtg     2700

aagaaaatga agaactactg gagacagctc ctgaacgcca agctgatcac ccagagaaag     2760

ttcgacaacc tgaccaaggc cgagagaggc gggctgagcg agctcgacaa agccggcttc     2820

atcaagagac agctggtgga aaccagacag atcaccaagc acgtggccca gatcctggac     2880

agcagaatga acaccaagta cgacgagaac gataagctga tcagagaggt gaaggtcatc     2940

accctgaaga gcaaactggt gagcgacttc agaaaggact tccagttcta caaggtgaga     3000

gagatcaata actaccatca cgctcatgac gcctacctga acgccgtcgt gggcaccgcc     3060

ctgatcaaga aataccccaa gctggagagc gagttcgtgt acggcgacta caaggtgtac     3120

gacgtgagaa agatgatcgc caagagcgag caggagatcg gcaaggccac cgccaagtac     3180

ttcttttaca gcaacatcat gaacttcttt aagaccgaga tcaccctggc caacggcgag     3240

atcagaaaga ggcccctgat cgaaaccaac ggcgaaaccg gcgagatcgt gtgggacaag     3300

ggcagagact tcgccaccgt gagaaaggtg ctgagcatgc cccaggtgaa catcgtgaag     3360

aaaaccgagg tgcagaccgg aggcttcagc aaggagagca tcctgcccaa gagaaacagc     3420

gacaagctga tcgccagaaa gaaagactgg gaccccaaga aatacggagg cttcgacagc     3480

cccaccgtgg cctacagcgt gctggtcgtg gccaaggtgg agaagggcaa gagcaagaaa     3540

ctgaagagcg tgaaggagct cctgggcatc accatcatgg agagatccag cttcgagaag     3600

aaccccatcg acttcctgga ggccaagggc tacaaggagg tgaagaaaga cctgattatc     3660

aagctgccca agtacagcct gttcgagctg gagaacggca gaaagagaat gctggccagc     3720

gccggcgagc tgcagaaggg caacgagctg gccctgccca gcaagtacgt gaacttcctg     3780

tacctggcca gccactacga gaagctgaag ggcagccccg aggacaacga gcagaagcag     3840

ctgttcgtgg agcagcacaa gcactacctg gacgaaatca ttgagcagat cagcgagttc     3900

agtaagagag tgatcctggc tgacgccaac ctggacaagg tgctgagcgc ctacaacaag     3960

cacagagaca agcccatcag agagcaggcc gagaacatca ttcacctgtt caccctgacc     4020

aacctgggcg cacccgcagc cttcaagtac ttcgacacca caatcgacag aaagagatac     4080

accagcacca aggaggtgct ggacgccacc ctgatccacc agagcatcac cggcctgtac     4140

gaaaccagaa tcgacctgtc acagcttggg ggtgacggat ccgctgctcc aaagaagaag     4200

cgtaaggtag attaa                                                      4215


<210>  19
<211>  4215
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  OMF-Cas9-O encoding sequence

<400>  19
atgccacctc ccaagaggcc caggctggac ctcgaggagc agaagctgat cagcgaggag       60

gacctgggag gaagcggaga taaaaagtat tctattggtt tagacatcgg caccaacagc      120

gtgggctggg ccgtgatcac cgacgagtac aaggtgccca gcaagaaatt caaggtgctg      180

ggcaacaccg acagacacag catcaagaaa aacctgatcg gcgccctgct cttcgactcc      240

ggcgaaaccg ccgaggccac cagactgaag agaaccgcca gacggagata caccagacgg      300

aagaatagaa tctgctacct gcaggagatc ttcagcaacg agatggccaa ggtggacgat      360

agcttctttc acagactgga agagagcttc ctggtggaag aggacaagaa acacgagaga      420

caccccatct tcggcaacat cgtggacgag gtggcctacc acgagaagta ccccaccatc      480

taccacctga gaaagaaact ggtggacagc accgacaagg ccgacctgag actgatctac      540

ctggcactgg cccacatgat caagttcaga ggccacttcc tgatcgaggg cgacctgaac      600

cccgacaaca gcgacgtgga caagctgttc atccagctgg tgcagaccta caaccagctg      660

ttcgaagaga accctatcaa cgccagcggc gtggacgcca aggccatcct gagcgccaga      720

ctcagcaaga gcagacggct ggagaacctg atcgcccagc tgcccggcga gaagaaaaac      780

ggcctgttcg gcaacctgat cgccctgagc ctgggcctga cccccaactt caagagcaac      840

ttcgacctgg ccgaggacgc caagctgcag ctgagcaagg acacctacga cgatgacctg      900

gacaacctcc tggcccagat cggcgaccag tacgccgacc tgttcctcgc agccaagaac      960

ctgagcgacg ccatcctcct gagcgacatc ctcagagtga acaccgagat caccaaggct     1020

cccctgagcg ccagcatgat caagagatac gacgagcacc atcaggacct gaccctcctg     1080

aaggccctcg tgagacaaca gctgcccgag aagtacaagg agatcttctt tgaccagagc     1140

aagaacggct acgccggcta catcgacgga ggcgccagtc aggaagagtt ctacaagttc     1200

atcaagccca tcctggagaa gatggacggc accgaagagc tgctcgtgaa gctgaacaga     1260

gaggacctgc tcagaaagca gagaaccttc gacaacggca gcatccccca ccagatccac     1320

ctgggcgagc tgcacgccat cctgagacgg caggaggact tctacccctt cctgaaggac     1380

aacagagaga agattgaaaa gatcctgacc ttcagaatcc cctactatgt gggccccctg     1440

gccagaggca acagcagatt cgcctggatg accaggaaga gcgaagagac aatcacacct     1500

tggaacttcg aagaggtggt cgacaaaggc gccagcgccc agagcttcat cgagagaatg     1560

accaacttcg acaagaacct gcccaacgag aaggtgctgc ccaagcacag cctcctgtac     1620

gagtacttca ccgtgtacaa cgagctgacc aaggtgaagt acgtgaccga gggcatgaga     1680

aagcctgcct ttctgagtgg cgagcagaag aaagccatcg tggacctgct cttcaagacc     1740

aacagaaaag tgaccgtgaa gcagctgaag gaggactact tcaagaaaat cgagtgcttc     1800

gacagcgtgg agatcagcgg cgtggaggac agattcaacg ccagcctggg cacctaccac     1860

gacctgctca agattatcaa agacaaggac ttcctggaca acgaagagaa cgaggacatc     1920

ctggaggaca tcgtgctgac actgaccctc ttcgaggaca gagagatgat cgaagagaga     1980

ctgaagacct acgcccacct gttcgatgac aaggtgatga agcagctgaa gagacggaga     2040

tacaccggct ggggcagact gagcagaaag ctgatcaacg gcatcagaga caagcagagc     2100

ggcaagacca tcctggactt cctgaagagc gacggcttcg ccaacagaaa cttcatgcag     2160

ctgatccacg atgacagcct gaccttcaag gaggacatcc agaaagccca agtgagcggg     2220

cagggcgaca gcctgcacga gcatatcgcc aacctggctg gcagccccgc catcaagaaa     2280

ggcatcctgc agaccgtgaa ggtcgtggac gagctggtca aggtgatggg cagacacaag     2340

cccgagaaca tcgtgattga gatggccaga gagaaccaga caacccagaa gggccagaag     2400

aacagcagag agagaatgaa gagaatcgaa gagggcatca aggagctggg cagccagatc     2460

ctgaaggagc accccgtgga gaacacccag ctgcagaacg agaagctgta cctgtattac     2520

ctgcagaacg gcagagacat gtacgtggac caggagctgg acatcaacag actgagcgat     2580

tacgacgtgg atcacatcgt cccccagagc ttcctgaagg atgacagcat cgataacaag     2640

gtgctgacca gaagcgacaa gaacagaggc aagagcgaca acgtgcccag cgaagaggtc     2700

gtgaagaaaa tgaagaacta ctggagacag ctcctgaacg ccaagctgat cacccagaga     2760

aagttcgaca acctgaccaa ggccgagaga ggcgggctga gcgagctcga caaagccggc     2820

ttcatcaaga gacagctggt ggaaaccaga cagatcacca agcacgtggc ccagatcctg     2880

gacagcagaa tgaacaccaa gtacgacgag aacgataagc tgatcagaga ggtgaaggtc     2940

atcaccctga agagcaaact ggtgagcgac ttcagaaagg acttccagtt ctacaaggtg     3000

agagagatca ataactacca tcacgctcat gacgcctacc tgaacgccgt cgtgggcacc     3060

gccctgatca agaaataccc caagctggag agcgagttcg tgtacggcga ctacaaggtg     3120

tacgacgtga gaaagatgat cgccaagagc gagcaggaga tcggcaaggc caccgccaag     3180

tacttctttt acagcaacat catgaacttc tttaagaccg agatcaccct ggccaacggc     3240

gagatcagaa agaggcccct gatcgaaacc aacggcgaaa ccggcgagat cgtgtgggac     3300

aagggcagag acttcgccac cgtgagaaag gtgctgagca tgccccaggt gaacatcgtg     3360

aagaaaaccg aggtgcagac cggaggcttc agcaaggaga gcatcctgcc caagagaaac     3420

agcgacaagc tgatcgccag aaagaaagac tgggacccca agaaatacgg aggcttcgac     3480

agccccaccg tggcctacag cgtgctggtc gtggccaagg tggagaaggg caagagcaag     3540

aaactgaaga gcgtgaagga gctcctgggc atcaccatca tggagagatc cagcttcgag     3600

aagaacccca tcgacttcct ggaggccaag ggctacaagg aggtgaagaa agacctgatt     3660

atcaagctgc ccaagtacag cctgttcgag ctggagaacg gcagaaagag aatgctggcc     3720

agcgccggcg agctgcagaa gggcaacgag ctggccctgc ccagcaagta cgtgaacttc     3780

ctgtacctgg ccagccacta cgagaagctg aagggcagcc ccgaggacaa cgagcagaag     3840

cagctgttcg tggagcagca caagcactac ctggacgaaa tcattgagca gatcagcgag     3900

ttcagtaaga gagtgatcct ggctgacgcc aacctggaca aggtgctgag cgcctacaac     3960

aagcacagag acaagcccat cagagagcag gccgagaaca tcattcacct gttcaccctg     4020

accaacctgg gcgcacccgc agccttcaag tacttcgaca ccacaatcga cagaaagaga     4080

tacaccagca ccaaggaggt gctggacgcc accctgatcc accagagcat caccggcctg     4140

tacgaaacca gaatcgacct gtcacagctt gggggtgacg gatcccctcc tcccaagagg     4200

cccaggctgg actaa                                                      4215


<210>  20
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Internal linker

<400>  20

Gly Ile His Gly Val Pro Ala Ala 
1               5               


<210>  21
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  flexible linker

<400>  21

Gly Gly Ser Gly 
1               


<210>  22
<211>  1371
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  partial sequence of Cas9

<400>  22

Asp Lys Lys Tyr Ser Ile Gly Leu Asp 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 Gly 
    1355                 1360                 1365             


Ser Ala  Ala 
    1370     


<210>  23
<211>  76
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  myc-Cas9 forward

<400>  23
aatttaccgg tcaaacatgg agcagaagct gatcagcgag gaggacctga tggccccaaa       60

gaagaagcgg aaggtc                                                       76


<210>  24
<211>  119
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  heiCas9 forward

<400>  24
aatttaccgg tttaccatgg agcagaagct gatcagcgag gaggacctgg gaggaagcgg       60

accacctccc aagaggccca ggctggacct cgaggataaa aagtattcta ttggtttag       119


<210>  25
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  pCS2+ backbone forward

<400>  25
gcctctagaa ctatagtgag tcg                                               23


<210>  26
<211>  44
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  hei-tag forward

<400>  26
cttgttcttt ttgcaggatc ccatttacca tggagcagaa gctg                        44


<210>  27
<211>  33
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Gam Mu-APOBEC1-Cas9n fragment forward

<400>  27
gacctcgagg ctaaaccagc aaaacgtatc aag                                    33


<210>  28
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cas9n-UGI fragment forward

<400>  28
gacacttctc aaggccctag                                                   20


<210>  29
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  2xUGI-oNLS forward

<400>  29
cagcttgggg gtgactctg                                                    19


<210>  30
<211>  66
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  heiCas9 reverse

<400>  30
aattttctag attagtccag cctgggcctc ttgggaggag gggatccgtc acccccaagc       60

tgtgac                                                                  66


<210>  31
<211>  38
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  myc-Cas9 reverse

<400>  31
aattttctag attacttttt cttttttgcc tggccggc                               38


<210>  32
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  pCS2+ backbone reverse

<400>  32
atgggatcct gcaaaaagaa caag                                              24


<210>  33
<211>  28
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  hei-tag reverse

<400>  33
gctggtttag cctcgaggtc cagcctgg                                          28


<210>  34
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Gam Mu-APOBEC1-Cas9n fragment reverse

<400>  34
ctagggcctt gagaagtgtc                                                   20


<210>  35
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cas9n-UGI fragment reverse

<400>  35
cagagtcacc cccaagctg                                                    19


<210>  36
<211>  69
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  2xUGI-oNLS reverse

<400>  36
cgactcacta tagttctaga ggcttagtcc agcctgggcc tcttgggagg gggagaacca       60

ccagagagc                                                               69


<210>  37
<211>  29
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oca2 fwd

<400>  37
gttaaaacag tttcttaaaa agaacagga                                         29


<210>  38
<211>  26
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oca2 rev

<400>  38
agcagaagaa atgactcaac attttg                                            26


<210>  39
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  MmPrx exon 6 crRNA

<400>  39
tcgtatccag acaccgtccc ggg                                               23


<210>  40
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  MmPrx exon 6 fwd

<400>  40
gagacactca ctccagaccc                                                   20


<210>  41
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  MmPrx exon 6 rev

<400>  41
actcagtaac ccaacagcca                                                   20


<210>  42
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Fig. 4 Upper

<400>  42
ggaaacccag gtggccattg cagga                                             25


<210>  43
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fig. 4 middle

<400>  43

Glu Thr Gln Val Ala Ile Ala Gly 
1               5               


<210>  44
<211>  12
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Fig. 4 lower

<400>  44
gaaatttagg tg                                                           12


<210>  45
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NLS8

<400>  45

Ala Pro Lys Lys Lys Arg Lys Val 
1               5               


<210>  46
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Internal linker 2

<400>  46

Val Pro Ala Ala 
1               


