                         SEQUENCE LISTING

<110>  CNRS
 
<120>  TARGETED-ANTIBACTERIAL-PLASMIDS COMBINING CONJUGATION AND CRISPR 
       /CAS SYSTEMS AND USES THEREOF

<130>  BIO20416 LESTERLIN / MC

<160>  28    

<170>  PatentIn version 3.3

<210>  1
<211>  772
<212>  DNA
<213>  Artificial

<220>
<223>  OriV of pBBR1 plasmid

<400>  1
gcttatctcc atgcggtagg ggtgccgcac ggttgcggca ccatgcgcaa tcagctgcaa     60

cttttcggca gcgcgacaac aattatgcgt tgcgtaaaag tggcagtcaa ttacagattt    120

tctttaacct acgcaatgag ctattgcggg gggtgccgca atgagctgtt gcgtaccccc    180

cttttttaag ttgttgattt ttaagtcttt cgcatttcgc cctatatcta gttctttggt    240

gcccaaagaa gggcacccct gcggggttcc cccacgcctt cggcgcggct ccccctccgg    300

caaaaagtgg cccctccggg gcttgttgat cgactgcgcg gccttcggcc ttgcccaagg    360

tggcgctgcc cccttggaac ccccgcactc gccgccgtga ggctcggggg gcaggcgggc    420

gggcttcgcc cttcgactgc ccccactcgc ataggcttgg gtcgttccag gcgcgtcaag    480

gccaagccgc tgcgcggtcg ctgcgcgagc cttgacccgc cttccacttg gtgtccaacc    540

ggcaagcgaa gcgcgcaggc cgcaggccgg aggcttttcc ccagagaaaa ttaaaaaaat    600

tgatggggca aggccgcagg ccgcgcagtt ggagccggtg ggtatgtggt cgaaggctgg    660

gtagccggtg ggcaatccct gtggtcaagc tcgtgggcag gcgcagcctg tccatcagct    720

tgtccagcag ggttgtccac gggccgagcg aagcgagcca gccggtggcc gc            772


<210>  2
<211>  109
<212>  DNA
<213>  Artificial

<220>
<223>  OriT of RP4 plasmid

<400>  2
gggcaggata ggtgaagtag gcccacccgc gagcgggtgt tccttcttca ctgtccctta     60

ttcgcacctg gcggtgctca acgggaatcc tgctctgcga ggctggccg                109


<210>  3
<211>  290
<212>  DNA
<213>  Artificial

<220>
<223>  oriT of F plasmid

<400>  3
aggctcaaca ggttggtggt tctcaccacc aaaagcacca caccccacgc aaaaacaagt     60

ttttgctgat ttttctttat aaatagagtg ttatgaaaaa ttagtttctc ttactctctt    120

tatgatattt aaaaaagcgg tgtcggcgcg gctacaacaa cgcgccgaca ccgttttgta    180

ggggtggtac tgactatttt tataaaaaac attattttat attaggggtg ctgctagcgg    240

cgcggtgtgt ttttttatag gataccgcta ggggcgctgc tagcggtgcg               290


<210>  4
<211>  1368
<212>  PRT
<213>  Streptococcus pyogenes

<400>  4

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>  5
<211>  1368
<212>  PRT
<213>  Artificial

<220>
<223>  Nickase

<400>  5

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>  6
<211>  1368
<212>  PRT
<213>  Artificial

<220>
<223>  Nickase

<400>  6

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 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>  7
<211>  4107
<212>  DNA
<213>  Artificial

<220>
<223>  Cas9 (addgene #44250)

<400>  7
atggataaga aatactcaat aggcttagat atcggcacaa atagcgtcgg atgggcggtg     60

atcactgatg aatataaggt tccgtctaaa aagttcaagg ttctgggaaa tacagaccgc    120

cacagtatca aaaaaaatct tataggggct cttttatttg acagtggaga gacagcggaa    180

gcgactcgtc tcaaacggac agctcgtaga aggtatacac gtcggaagaa tcgtatttgt    240

tatctacagg agattttttc aaatgagatg gcgaaagtag atgatagttt ctttcatcga    300

cttgaagagt cttttttggt ggaagaagac aagaagcatg aacgtcatcc tatttttgga    360

aatatagtag atgaagttgc ttatcatgag aaatatccaa ctatctatca tctgcgaaaa    420

aaattggtag attctactga taaagcggat ttgcgcttaa tctatttggc cttagcgcat    480

atgattaagt ttcgtggtca ttttttgatt gagggagatt taaatcctga taatagtgat    540

gtggacaaac tatttatcca gttggtacaa acctacaatc aattatttga agaaaaccct    600

attaacgcaa gtggagtaga tgctaaagcg attctttctg cacgattgag taaatcaaga    660

cgattagaaa atctcattgc tcagctcccc ggtgagaaga aaaatggctt atttgggaat    720

ctcattgctt tgtcattggg tttgacccct aattttaaat caaattttga tttggcagaa    780

gatgctaaat tacagctttc aaaagatact tacgatgatg atttagataa tttattggcg    840

caaattggag atcaatatgc tgatttgttt ttggcagcta agaatttatc agatgctatt    900

ttactttcag atatcctaag agtaaatact gaaataacta aggctcccct atcagcttca    960

atgattaaac gctacgatga acatcatcaa gacttgactc ttttaaaagc tttagttcga   1020

caacaacttc cagaaaagta taaagaaatc ttttttgatc aatcaaaaaa cggatatgca   1080

ggttatattg atgggggagc tagccaagaa gaattttata aatttatcaa accaatttta   1140

gaaaaaatgg atggtactga ggaattattg gtgaaactaa atcgtgaaga tttgctgcgc   1200

aagcaacgga cctttgacaa cggctctatt ccccatcaaa ttcacttggg tgagctgcat   1260

gctattttga gaagacaaga agacttttat ccatttttaa aagacaatcg tgagaagatt   1320

gaaaaaatct tgacttttcg aattccttat tatgttggtc cattggcgcg tggcaatagt   1380

cgttttgcat ggatgactcg gaagtctgaa gaaacaatta ccccatggaa ttttgaagaa   1440

gttgtcgata aaggtgcttc agctcaatca tttattgaac gcatgacaaa ctttgataaa   1500

aatcttccaa atgaaaaagt actaccaaaa catagtttgc tttatgagta ttttacggtt   1560

tataacgaat tgacaaaggt caaatatgtt actgaaggaa tgcgaaaacc agcatttctt   1620

tcaggtgaac agaagaaagc cattgttgat ttactcttca aaacaaatcg aaaagtaacc   1680

gttaagcaat taaaagaaga ttatttcaaa aaaatagaat gttttgatag tgttgaaatt   1740

tcaggagttg aagatagatt taatgcttca ttaggtacct accatgattt gctaaaaatt   1800

attaaagata aagatttttt ggataatgaa gaaaatgaag atatcttaga ggatattgtt   1860

ttaacattga ccttatttga agatagggag atgattgagg aaagacttaa aacatatgct   1920

cacctctttg atgataaggt gatgaaacag cttaaacgtc gccgttatac tggttgggga   1980

cgtttgtctc gaaaattgat taatggtatt agggataagc aatctggcaa aacaatatta   2040

gattttttga aatcagatgg ttttgccaat cgcaatttta tgcagctgat ccatgatgat   2100

agtttgacat ttaaagaaga cattcaaaaa gcacaagtgt ctggacaagg cgatagttta   2160

catgaacata ttgcaaattt agctggtagc cctgctatta aaaaaggtat tttacagact   2220

gtaaaagttg ttgatgaatt ggtcaaagta atggggcggc ataagccaga aaatatcgtt   2280

attgaaatgg cacgtgaaaa tcagacaact caaaagggcc agaaaaattc gcgagagcgt   2340

atgaaacgaa tcgaagaagg tatcaaagaa ttaggaagtc agattcttaa agagcatcct   2400

gttgaaaata ctcaattgca aaatgaaaag ctctatctct attatctcca aaatggaaga   2460

gacatgtatg tggaccaaga attagatatt aatcgtttaa gtgattatga tgtcgatcac   2520

attgttccac aaagtttcct taaagacgat tcaatagaca ataaggtctt aacgcgttct   2580

gataaaaatc gtggtaaatc ggataacgtt ccaagtgaag aagtagtcaa aaagatgaaa   2640

aactattgga gacaacttct aaacgccaag ttaatcactc aacgtaagtt tgataattta   2700

acgaaagctg aacgtggagg tttgagtgaa cttgataaag ctggttttat caaacgccaa   2760

ttggttgaaa ctcgccaaat cactaagcat gtggcacaaa ttttggatag tcgcatgaat   2820

actaaatacg atgaaaatga taaacttatt cgagaggtta aagtgattac cttaaaatct   2880

aaattagttt ctgacttccg aaaagatttc caattctata aagtacgtga gattaacaat   2940

taccatcatg cccatgatgc gtatctaaat gccgtcgttg gaactgcttt gattaagaaa   3000

tatccaaaac ttgaatcgga gtttgtctat ggtgattata aagtttatga tgttcgtaaa   3060

atgattgcta agtctgagca agaaataggc aaagcaaccg caaaatattt cttttactct   3120

aatatcatga acttcttcaa aacagaaatt acacttgcaa atggagagat tcgcaaacgc   3180

cctctaatcg aaactaatgg ggaaactgga gaaattgtct gggataaagg gcgagatttt   3240

gccacagtgc gcaaagtatt gtccatgccc caagtcaata ttgtcaagaa aacagaagta   3300

cagacaggcg gattctccaa ggagtcaatt ttaccaaaaa gaaattcgga caagcttatt   3360

gctcgtaaaa aagactggga tccaaaaaaa tatggtggtt ttgatagtcc aacggtagct   3420

tattcagtcc tagtggttgc taaggtggaa aaagggaaat cgaagaagtt aaaatccgtt   3480

aaagagttac tagggatcac aattatggaa agaagttcct ttgaaaaaaa tccgattgac   3540

tttttagaag ctaaaggata taaggaagtt aaaaaagact taatcattaa actacctaaa   3600

tatagtcttt ttgagttaga aaacggtcgt aaacggatgc tggctagtgc cggagaatta   3660

caaaaaggaa atgagctggc tctgccaagc aaatatgtga attttttata tttagctagt   3720

cattatgaaa agttgaaggg tagtccagaa gataacgaac aaaaacaatt gtttgtggag   3780

cagcataagc attatttaga tgagattatt gagcaaatca gtgaattttc taagcgtgtt   3840

attttagcag atgccaattt agataaagtt cttagtgcat ataacaaaca tagagacaaa   3900

ccaatacgtg aacaagcaga aaatattatt catttattta cgttgacgaa tcttggagct   3960

cccgctgctt ttaaatattt tgatacaaca attgatcgta aacgatatac gtctacaaaa   4020

gaagttttag atgccactct tatccatcaa tccatcactg gtctttatga aacacgcatt   4080

gatttgagtc agctaggagg tgactaa                                       4107


<210>  8
<211>  4107
<212>  DNA
<213>  Artificial

<220>
<223>  dCas9 (addgene #44249)

<400>  8
atggataaga aatactcaat aggcttagct atcggcacaa atagcgtcgg atgggcggtg     60

atcactgatg aatataaggt tccgtctaaa aagttcaagg ttctgggaaa tacagaccgc    120

cacagtatca aaaaaaatct tataggggct cttttatttg acagtggaga gacagcggaa    180

gcgactcgtc tcaaacggac agctcgtaga aggtatacac gtcggaagaa tcgtatttgt    240

tatctacagg agattttttc aaatgagatg gcgaaagtag atgatagttt ctttcatcga    300

cttgaagagt cttttttggt ggaagaagac aagaagcatg aacgtcatcc tatttttgga    360

aatatagtag atgaagttgc ttatcatgag aaatatccaa ctatctatca tctgcgaaaa    420

aaattggtag attctactga taaagcggat ttgcgcttaa tctatttggc cttagcgcat    480

atgattaagt ttcgtggtca ttttttgatt gagggagatt taaatcctga taatagtgat    540

gtggacaaac tatttatcca gttggtacaa acctacaatc aattatttga agaaaaccct    600

attaacgcaa gtggagtaga tgctaaagcg attctttctg cacgattgag taaatcaaga    660

cgattagaaa atctcattgc tcagctcccc ggtgagaaga aaaatggctt atttgggaat    720

ctcattgctt tgtcattggg tttgacccct aattttaaat caaattttga tttggcagaa    780

gatgctaaat tacagctttc aaaagatact tacgatgatg atttagataa tttattggcg    840

caaattggag atcaatatgc tgatttgttt ttggcagcta agaatttatc agatgctatt    900

ttactttcag atatcctaag agtaaatact gaaataacta aggctcccct atcagcttca    960

atgattaaac gctacgatga acatcatcaa gacttgactc ttttaaaagc tttagttcga   1020

caacaacttc cagaaaagta taaagaaatc ttttttgatc aatcaaaaaa cggatatgca   1080

ggttatattg atgggggagc tagccaagaa gaattttata aatttatcaa accaatttta   1140

gaaaaaatgg atggtactga ggaattattg gtgaaactaa atcgtgaaga tttgctgcgc   1200

aagcaacgga cctttgacaa cggctctatt ccccatcaaa ttcacttggg tgagctgcat   1260

gctattttga gaagacaaga agacttttat ccatttttaa aagacaatcg tgagaagatt   1320

gaaaaaatct tgacttttcg aattccttat tatgttggtc cattggcgcg tggcaatagt   1380

cgttttgcat ggatgactcg gaagtctgaa gaaacaatta ccccatggaa ttttgaagaa   1440

gttgtcgata aaggtgcttc agctcaatca tttattgaac gcatgacaaa ctttgataaa   1500

aatcttccaa atgaaaaagt actaccaaaa catagtttgc tttatgagta ttttacggtt   1560

tataacgaat tgacaaaggt caaatatgtt actgaaggaa tgcgaaaacc agcatttctt   1620

tcaggtgaac agaagaaagc cattgttgat ttactcttca aaacaaatcg aaaagtaacc   1680

gttaagcaat taaaagaaga ttatttcaaa aaaatagaat gttttgatag tgttgaaatt   1740

tcaggagttg aagatagatt taatgcttca ttaggtacct accatgattt gctaaaaatt   1800

attaaagata aagatttttt ggataatgaa gaaaatgaag atatcttaga ggatattgtt   1860

ttaacattga ccttatttga agatagggag atgattgagg aaagacttaa aacatatgct   1920

cacctctttg atgataaggt gatgaaacag cttaaacgtc gccgttatac tggttgggga   1980

cgtttgtctc gaaaattgat taatggtatt agggataagc aatctggcaa aacaatatta   2040

gattttttga aatcagatgg ttttgccaat cgcaatttta tgcagctgat ccatgatgat   2100

agtttgacat ttaaagaaga cattcaaaaa gcacaagtgt ctggacaagg cgatagttta   2160

catgaacata ttgcaaattt agctggtagc cctgctatta aaaaaggtat tttacagact   2220

gtaaaagttg ttgatgaatt ggtcaaagta atggggcggc ataagccaga aaatatcgtt   2280

attgaaatgg cacgtgaaaa tcagacaact caaaagggcc agaaaaattc gcgagagcgt   2340

atgaaacgaa tcgaagaagg tatcaaagaa ttaggaagtc agattcttaa agagcatcct   2400

gttgaaaata ctcaattgca aaatgaaaag ctctatctct attatctcca aaatggaaga   2460

gacatgtatg tggaccaaga attagatatt aatcgtttaa gtgattatga tgtcgatgcc   2520

attgttccac aaagtttcct taaagacgat tcaatagaca ataaggtctt aacgcgttct   2580

gataaaaatc gtggtaaatc ggataacgtt ccaagtgaag aagtagtcaa aaagatgaaa   2640

aactattgga gacaacttct aaacgccaag ttaatcactc aacgtaagtt tgataattta   2700

acgaaagctg aacgtggagg tttgagtgaa cttgataaag ctggttttat caaacgccaa   2760

ttggttgaaa ctcgccaaat cactaagcat gtggcacaaa ttttggatag tcgcatgaat   2820

actaaatacg atgaaaatga taaacttatt cgagaggtta aagtgattac cttaaaatct   2880

aaattagttt ctgacttccg aaaagatttc caattctata aagtacgtga gattaacaat   2940

taccatcatg cccatgatgc gtatctaaat gccgtcgttg gaactgcttt gattaagaaa   3000

tatccaaaac ttgaatcgga gtttgtctat ggtgattata aagtttatga tgttcgtaaa   3060

atgattgcta agtctgagca agaaataggc aaagcaaccg caaaatattt cttttactct   3120

aatatcatga acttcttcaa aacagaaatt acacttgcaa atggagagat tcgcaaacgc   3180

cctctaatcg aaactaatgg ggaaactgga gaaattgtct gggataaagg gcgagatttt   3240

gccacagtgc gcaaagtatt gtccatgccc caagtcaata ttgtcaagaa aacagaagta   3300

cagacaggcg gattctccaa ggagtcaatt ttaccaaaaa gaaattcgga caagcttatt   3360

gctcgtaaaa aagactggga tccaaaaaaa tatggtggtt ttgatagtcc aacggtagct   3420

tattcagtcc tagtggttgc taaggtggaa aaagggaaat cgaagaagtt aaaatccgtt   3480

aaagagttac tagggatcac aattatggaa agaagttcct ttgaaaaaaa tccgattgac   3540

tttttagaag ctaaaggata taaggaagtt aaaaaagact taatcattaa actacctaaa   3600

tatagtcttt ttgagttaga aaacggtcgt aaacggatgc tggctagtgc cggagaatta   3660

caaaaaggaa atgagctggc tctgccaagc aaatatgtga attttttata tttagctagt   3720

cattatgaaa agttgaaggg tagtccagaa gataacgaac aaaaacaatt gtttgtggag   3780

cagcataagc attatttaga tgagattatt gagcaaatca gtgaattttc taagcgtgtt   3840

attttagcag atgccaattt agataaagtt cttagtgcat ataacaaaca tagagacaaa   3900

ccaatacgtg aacaagcaga aaatattatt catttattta cgttgacgaa tcttggagct   3960

cccgctgctt ttaaatattt tgatacaaca attgatcgta aacgatatac gtctacaaaa   4020

gaagttttag atgccactct tatccatcaa tccatcactg gtctttatga aacacgcatt   4080

gatttgagtc agctaggagg tgactaa                                       4107


<210>  9
<211>  53
<212>  DNA
<213>  Artificial

<220>
<223>  promoter

<400>  9
tttacggcta gctcagccct aggtattatg ctagcagatc taaagaggag aaa            53


<210>  10
<211>  35
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  10
tagtccatta cggtcaatcc gccgtttgtt cccag                                35


<210>  11
<211>  35
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  11
aaactgggaa caaacggcgg attgaccgta atgga                                35


<210>  12
<211>  25
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  12
tagtcaccaa aaacacagcc gatag                                           25


<210>  13
<211>  25
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  13
aaactatcgg ctgtgttttt ggtga                                           25


<210>  14
<211>  25
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  14
tagttgtttt tcatgttgtc acccg                                           25


<210>  15
<211>  25
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  15
aaacgggtga caacatgaaa aacaa                                           25


<210>  16
<211>  25
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  16
tagttgtaat cacaatgatg aaaag                                           25


<210>  17
<211>  25
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  17
aaacttttca tcattgtgat tacaa                                           25


<210>  18
<211>  25
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  18
tagtagcgcc aaccgatatc accag                                           25


<210>  19
<211>  25
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  19
aaactggtga tatcggttgg cgcta                                           25


<210>  20
<211>  22
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  20
tagttgccat cactactgtg cg                                              22


<210>  21
<211>  22
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  21
aaacgcacag tagtgatggc aa                                              22


<210>  22
<211>  22
<212>  DNA
<213>  Artificial

<220>
<223>  space sequence

<400>  22
tagttggcgt tgaagacgac gg                                              22


<210>  23
<211>  22
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  23
aaaccgtcgt cttcaacgcc aa                                              22


<210>  24
<211>  22
<212>  DNA
<213>  Artificial

<220>
<223>  spacer sequence

<400>  24
tagtgatatc aaagtggtta tg                                              22


<210>  25
<211>  76
<212>  DNA
<213>  Artificial

<220>
<223>  tracrRNA sequence

<400>  25
gttttagagc tagaaatagc aagttaaaat aaggctagtc cgttatcaac ttgaaaaagt     60

ggcaccgagt cggtgc                                                     76


<210>  26
<211>  35
<212>  DNA
<213>  Artificial

<220>
<223>  promoter

<400>  26
ttgacagcta gctcagtcct aggtataata ctagt                                35


<210>  27
<211>  7631
<212>  DNA
<213>  Artificial

<220>
<223>  TAPKn-Cas9-nsp

<400>  27
atctttgaca gctagctcag tcctaggtat aatactagtg aagagcaccg gtgctcttcg     60

ttttagagct agaaatagca agttaaaata aggctagtcc gttatcaact tgaaaaagtg    120

gcaccgagtc ggtgcttttt ttgaagcttg ggcccgaaca aaaaaaaacc ccgcccctga    180

cagggcgggg ttttttttgt ttgtcggtga actggatcct taccagctgg gcgcgccccc    240

cctacgggct tgctctccgg gcttcgccct gcgcggtcgc tgcgctccct tgccagcccg    300

tggatatgtg gacgatggcc gcgagcggcc accggctggc tcgcttcgct cggcccgtgg    360

acaaccctgc tggacaagct gatggacagg ctgcgcctgc ccacgagctt gaccacaggg    420

attgcccacc ggctacccag ccttcgacca catacccacc ggctccaact gcgcggcctg    480

cggccttgcc ccatcaattt ttttaatttt ctctggggaa aagcctccgg cctgcggcct    540

gcgcgcttcg cttgccggtt ggacaccaag tggaaggcgg gtcaaggctc gcgcagcgac    600

cgcgcagcgg cttggccttg acgcgcctgg aacgacccaa gcctatgcga gtgggggcag    660

tcgaagggcg aagcccgccc gcctgccccc cgagcctcac ggcggcgagt gcgggggttc    720

caagggggca gcgccacctt gggcaaggcc gaaggccgcg cagtcgatca acaagccccg    780

gaggggccac tttttgccgg agggggagcc gcgccgaagg cgtgggggaa ccccgcaggg    840

gtgcccttct ttgggcacca aagaactaga tatagggcga aatgcgaaag acttaaaaat    900

caacaactta aaaaaggggg gtacgcaaca gctcattgcg gcaccccccg caatagctca    960

ttgcgtaggt taaagaaaat ctgtaattga ctgccacttt tacgcaacgc ataattgttg   1020

tcgcgctgcc gaaaagttgc agctgattgc gcatggtgcc gcaaccgtgc ggcaccccta   1080

ccgcatggag ataagcatgg ccacgcagtc cagagaaatc ggcattcaag ccaagaacaa   1140

gcccggtcac tgggtgcaaa cggaacgcaa agcgcatgag gcgtgggccg ggcttattgc   1200

gaggaaaccc acggcggcaa tgctgctgca tcacctcgtg gcgcagatgg gccaccagaa   1260

cgccgtggtg gtcagccaga agacactttc caagctcatc ggacgttctt tgcggacggt   1320

ccaatacgca gtcaaggact tggtggccga gcgctggatc tccgtcgtga agctcaacgg   1380

ccccggcacc gtgtcggcct acgtggtcaa tgaccgcgtg gcgtggggcc agccccgcga   1440

ccagttgcgc ctgtcggtgt tcagtgccgc cgtggtggtt gatcacgacg accaggacga   1500

atcgctgttg gggcatggcg acctgcgccg catcccgacc ctgtatccgg gcgagcagca   1560

actaccgacc ggccccggcg aggagccgcc cagccagccc ggcattccgg gcatggaacc   1620

agacctgcca gccttgaccg aaacggagga atgggaacgg cgcgggcagc agcgcctgcc   1680

gatgcccgat gagccgtgtt ttctggacga tggcgagccg ttggagccgc cgacacgggt   1740

aacgctgccg cgccggtagg gcatgcaaac agggacgcac cgctagcagc gcccctagcg   1800

gtatcctata aaaaaacaca ccgcgccgct agcagcaccc ctaatataaa ataatgtttt   1860

ttataaaaat agtcagtacc acccctacaa aacggtgtcg gcgcgttgtt gtagccgcgc   1920

cgacaccgct tttttaaata tcataaagag agtaagagaa actaattttt cataacactc   1980

tatttataaa gaaaaatcag caaaaacttg tttttgcgtg gggtgtggtg cttttggtgg   2040

tgagaaccac caacctgttg agcctttttg tggagcgcgc ggaccgcggt ccagagagcg   2100

ttcaccgaca aacaacagat aaaacgaaag gcccagtctt tcgactgagc ctttcgtttt   2160

atttgatgcc tggagatcct tactcgagtt agtcacctcc tagctgactc aaatcaatgc   2220

gtgtttcata aagaccagtg atggattgat ggataagagt ggcatctaaa acttcttttg   2280

tagacgtata tcgtttacga tcaattgttg tatcaaaata tttaaaagca gcgggagctc   2340

caagattcgt caacgtaaat aaatgaataa tattttctgc ttgttcacgt attggtttgt   2400

ctctatgttt gttatatgca ctaagaactt tatctaaatt ggcatctgct aaaataacac   2460

gcttagaaaa ttcactgatt tgctcaataa tctcatctaa ataatgctta tgctgctcca   2520

caaacaattg tttttgttcg ttatcttctg gactaccctt caacttttca taatgactag   2580

ctaaatataa aaaattcaca tatttgcttg gcagagccag ctcatttcct ttttgtaatt   2640

ctccggcact agccagcatc cgtttacgac cgttttctaa ctcaaaaaga ctatatttag   2700

gtagtttaat gattaagtct tttttaactt ccttatatcc tttagcttct aaaaagtcaa   2760

tcggattttt ttcaaaggaa cttctttcca taattgtgat ccctagtaac tctttaacgg   2820

attttaactt cttcgatttc cctttttcca ccttagcaac cactaggact gaataagcta   2880

ccgttggact atcaaaacca ccatattttt ttggatccca gtctttttta cgagcaataa   2940

gcttgtccga atttcttttt ggtaaaattg actccttgga gaatccgcct gtctgtactt   3000

ctgttttctt gacaatattg acttggggca tggacaatac tttgcgcact gtggcaaaat   3060

ctcgcccttt atcccagaca atttctccag tttccccatt agtttcgatt agagggcgtt   3120

tgcgaatctc tccatttgca agtgtaattt ctgttttgaa gaagttcatg atattagagt   3180

aaaagaaata ttttgcggtt gctttgccta tttcttgctc agacttagca atcattttac   3240

gaacatcata aactttataa tcaccataga caaactccga ttcaagtttt ggatatttct   3300

taatcaaagc agttccaacg acggcattta gatacgcatc atgggcatga tggtaattgt   3360

taatctcacg tactttatag aattggaaat cttttcggaa gtcagaaact aatttagatt   3420

ttaaggtaat cactttaacc tctcgaataa gtttatcatt ttcatcgtat ttagtattca   3480

tgcgactatc caaaatttgt gccacatgct tagtgatttg gcgagtttca accaattggc   3540

gtttgataaa accagcttta tcaagttcac tcaaacctcc acgttcagct ttcgttaaat   3600

tatcaaactt acgttgagtg attaacttgg cgtttagaag ttgtctccaa tagtttttca   3660

tctttttgac tacttcttca cttggaacgt tatccgattt accacgattt ttatcagaac   3720

gcgttaagac cttattgtct attgaatcgt ctttaaggaa actttgtgga acaatgtgat   3780

cgacatcata atcacttaaa cgattaatat ctaattcttg gtccacatac atgtctcttc   3840

cattttggag ataatagaga tagagctttt cattttgcaa ttgagtattt tcaacaggat   3900

gctctttaag aatctgactt cctaattctt tgataccttc ttcgattcgt ttcatacgct   3960

ctcgcgaatt tttctggccc ttttgagttg tctgattttc acgtgccatt tcaataacga   4020

tattttctgg cttatgccgc cccattactt tgaccaattc atcaacaact tttacagtct   4080

gtaaaatacc ttttttaata gcagggctac cagctaaatt tgcaatatgt tcatgtaaac   4140

tatcgccttg tccagacact tgtgcttttt gaatgtcttc tttaaatgtc aaactatcat   4200

catggatcag ctgcataaaa ttgcgattgg caaaaccatc tgatttcaaa aaatctaata   4260

ttgttttgcc agattgctta tccctaatac cattaatcaa ttttcgagac aaacgtcccc   4320

aaccagtata acggcgacgt ttaagctgtt tcatcacctt atcatcaaag aggtgagcat   4380

atgttttaag tctttcctca atcatctccc tatcttcaaa taaggtcaat gttaaaacaa   4440

tatcctctaa gatatcttca ttttcttcat tatccaaaaa atctttatct ttaataattt   4500

ttagcaaatc atggtaggta cctaatgaag cattaaatct atcttcaact cctgaaattt   4560

caacactatc aaaacattct atttttttga aataatcttc ttttaattgc ttaacggtta   4620

cttttcgatt tgttttgaag agtaaatcaa caatggcttt cttctgttca cctgaaagaa   4680

atgctggttt tcgcattcct tcagtaacat atttgacctt tgtcaattcg ttataaaccg   4740

taaaatactc ataaagcaaa ctatgttttg gtagtacttt ttcatttgga agatttttat   4800

caaagtttgt catgcgttca ataaatgatt gagctgaagc acctttatcg acaacttctt   4860

caaaattcca tggggtaatt gtttcttcag acttccgagt catccatgca aaacgactat   4920

tgccacgcgc caatggacca acataataag gaattcgaaa agtcaagatt ttttcaatct   4980

tctcacgatt gtcttttaaa aatggataaa agtcttcttg tcttctcaaa atagcatgca   5040

gctcacccaa gtgaatttga tggggaatag agccgttgtc aaaggtccgt tgcttgcgca   5100

gcaaatcttc acgatttagt ttcaccaata attcctcagt accatccatt ttttctaaaa   5160

ttggtttgat aaatttataa aattcttctt ggctagctcc cccatcaata taacctgcat   5220

atccgttttt tgattgatca aaaaagattt ctttatactt ttctggaagt tgttgtcgaa   5280

ctaaagcttt taaaagagtc aagtcttgat gatgttcatc gtagcgttta atcattgaag   5340

ctgatagggg agccttagtt atttcagtat ttactcttag gatatctgaa agtaaaatag   5400

catctgataa attcttagct gccaaaaaca aatcagcata ttgatctcca atttgcgcca   5460

ataaattatc taaatcatca tcgtaagtat cttttgaaag ctgtaattta gcatcttctg   5520

ccaaatcaaa atttgattta aaattagggg tcaaacccaa tgacaaagca atgagattcc   5580

caaataagcc atttttcttc tcaccgggga gctgagcaat gagattttct aatcgtcttg   5640

atttactcaa tcgtgcagaa agaatcgctt tagcatctac tccacttgcg ttaatagggt   5700

tttcttcaaa taattgattg taggtttgta ccaactggat aaatagtttg tccacatcac   5760

tattatcagg atttaaatct ccctcaatca aaaaatgacc acgaaactta atcatatgcg   5820

ctaaggccaa atagattaag cgcaaatccg ctttatcagt agaatctacc aatttttttc   5880

gcagatgata gatagttgga tatttctcat gataagcaac ttcatctact atatttccaa   5940

aaataggatg acgttcatgc ttcttgtctt cttccaccaa aaaagactct tcaagtcgat   6000

gaaagaaact atcatctact ttcgccatct catttgaaaa aatctcctgt agataacaaa   6060

tacgattctt ccgacgtgta taccttctac gagctgtccg tttgagacga gtcgcttccg   6120

ctgtctctcc actgtcaaat aaaagagccc ctataagatt ttttttgata ctgtggcggt   6180

ctgtatttcc cagaaccttg aactttttag acggaacctt atattcatca gtgatcaccg   6240

cccatccgac gctatttgtg ccgatatcta agcctattga gtatttctta tccatagatc   6300

ctttctcctc tttagatctg ctagcataat acctagggct gagctagccg taaatgaggt   6360

ttcagcaaaa aacccctcaa gacccgttta gaggccccaa ggggttatgc tagttattgc   6420

tcagcggatt aattattaga aaaattcatc cagcatcaga tgaaattgca gtttgttcat   6480

atccggatta tcaatgccat atttctgaaa cagacgtttt tgcaggctcg ggctaaattc   6540

gcccaggcag ttccacagaa tggccagatc ctgataacga tccgcaatgc ccacacggcc   6600

cacatcaatg cagccaatca gtttgccttc atcgaaaatc aggttatcca ggctaaaatc   6660

gccgtgggtc accacgctat ccgggctaaa cggcagcagt ttatgcattt ctttccacac   6720

ctgttccacc ggccagccgt tacgttcatc atcaaaatcg ctcgcatcca ccaggccgtt   6780

gttcatacgg ctctgcgcct gggccagacg aaacacacga tcgctgttaa acgggcagtt   6840

gcacaccgga atgctatgca gacgacgcag aaacacggcc agcgcatcca caatgttttc   6900

gccgctatcc ggatattctt ccagcacctg aaacgcggtt ttgcccggaa tcgcggtggt   6960

cagcagccac gcatcatccg gggtgcgaat aaaatgttta atggtcggca gcggcataaa   7020

ttcggtcagc cagttcagac gcaccatttc atcggtcaca tcgttcgcca cgctgccttt   7080

gccatgtttc agaaacagtt ccggcgcatc cggtttgcca tacagacgat aaatggtcgc   7140

gccgctctga cccacgttat cacgcgccca tttatagcca tacagatccg catccatgtt   7200

gctgttcaga cgcggacggc tacagctcgt ttcacgctga atatggctca taacacccct   7260

tgtattactg tttatgtaag cagacagttt tattgttcat gatgatatat ttttatcttg   7320

tgcaatgtaa catcagagat tttgagacac aaatttaaat cgtaattatt ggggacccct   7380

ggattctcac caataaaaaa cgcccggcgg caaccgagcg ttctgaacaa atccagatgg   7440

agttctgagg tcattactgg atctatcaac aggagtccaa gactagtcgc cagggttttc   7500

ccagtcacga cgcggccgca agcttgcatg cctgcaggtc gactctagag gatccccggg   7560

taccgagctc gaattcgcgc ggccgcggcc taggcggcct cctgtgtgaa attgttatcc   7620

gctttaatta a                                                        7631


<210>  28
<211>  7631
<212>  DNA
<213>  Artificial

<220>
<223>  TAPKn-dCas9-nsp

<400>  28
atctttgaca gctagctcag tcctaggtat aatactagtg aagagcaccg gtgctcttcg     60

ttttagagct agaaatagca agttaaaata aggctagtcc gttatcaact tgaaaaagtg    120

gcaccgagtc ggtgcttttt ttgaagcttg ggcccgaaca aaaaaaaacc ccgcccctga    180

cagggcgggg ttttttttgt ttgtcggtga actggatcct taccagctgg gcgcgccccc    240

cctacgggct tgctctccgg gcttcgccct gcgcggtcgc tgcgctccct tgccagcccg    300

tggatatgtg gacgatggcc gcgagcggcc accggctggc tcgcttcgct cggcccgtgg    360

acaaccctgc tggacaagct gatggacagg ctgcgcctgc ccacgagctt gaccacaggg    420

attgcccacc ggctacccag ccttcgacca catacccacc ggctccaact gcgcggcctg    480

cggccttgcc ccatcaattt ttttaatttt ctctggggaa aagcctccgg cctgcggcct    540

gcgcgcttcg cttgccggtt ggacaccaag tggaaggcgg gtcaaggctc gcgcagcgac    600

cgcgcagcgg cttggccttg acgcgcctgg aacgacccaa gcctatgcga gtgggggcag    660

tcgaagggcg aagcccgccc gcctgccccc cgagcctcac ggcggcgagt gcgggggttc    720

caagggggca gcgccacctt gggcaaggcc gaaggccgcg cagtcgatca acaagccccg    780

gaggggccac tttttgccgg agggggagcc gcgccgaagg cgtgggggaa ccccgcaggg    840

gtgcccttct ttgggcacca aagaactaga tatagggcga aatgcgaaag acttaaaaat    900

caacaactta aaaaaggggg gtacgcaaca gctcattgcg gcaccccccg caatagctca    960

ttgcgtaggt taaagaaaat ctgtaattga ctgccacttt tacgcaacgc ataattgttg   1020

tcgcgctgcc gaaaagttgc agctgattgc gcatggtgcc gcaaccgtgc ggcaccccta   1080

ccgcatggag ataagcatgg ccacgcagtc cagagaaatc ggcattcaag ccaagaacaa   1140

gcccggtcac tgggtgcaaa cggaacgcaa agcgcatgag gcgtgggccg ggcttattgc   1200

gaggaaaccc acggcggcaa tgctgctgca tcacctcgtg gcgcagatgg gccaccagaa   1260

cgccgtggtg gtcagccaga agacactttc caagctcatc ggacgttctt tgcggacggt   1320

ccaatacgca gtcaaggact tggtggccga gcgctggatc tccgtcgtga agctcaacgg   1380

ccccggcacc gtgtcggcct acgtggtcaa tgaccgcgtg gcgtggggcc agccccgcga   1440

ccagttgcgc ctgtcggtgt tcagtgccgc cgtggtggtt gatcacgacg accaggacga   1500

atcgctgttg gggcatggcg acctgcgccg catcccgacc ctgtatccgg gcgagcagca   1560

actaccgacc ggccccggcg aggagccgcc cagccagccc ggcattccgg gcatggaacc   1620

agacctgcca gccttgaccg aaacggagga atgggaacgg cgcgggcagc agcgcctgcc   1680

gatgcccgat gagccgtgtt ttctggacga tggcgagccg ttggagccgc cgacacgggt   1740

aacgctgccg cgccggtagg gcatgcaaac agggacgcac cgctagcagc gcccctagcg   1800

gtatcctata aaaaaacaca ccgcgccgct agcagcaccc ctaatataaa ataatgtttt   1860

ttataaaaat agtcagtacc acccctacaa aacggtgtcg gcgcgttgtt gtagccgcgc   1920

cgacaccgct tttttaaata tcataaagag agtaagagaa actaattttt cataacactc   1980

tatttataaa gaaaaatcag caaaaacttg tttttgcgtg gggtgtggtg cttttggtgg   2040

tgagaaccac caacctgttg agcctttttg tggagcgcgc ggaccgcggt ccagagagcg   2100

ttcaccgaca aacaacagat aaaacgaaag gcccagtctt tcgactgagc ctttcgtttt   2160

atttgatgcc tggagatcct tactcgagtt agtcacctcc tagctgactc aaatcaatgc   2220

gtgtttcata aagaccagtg atggattgat ggataagagt ggcatctaaa acttcttttg   2280

tagacgtata tcgtttacga tcaattgttg tatcaaaata tttaaaagca gcgggagctc   2340

caagattcgt caacgtaaat aaatgaataa tattttctgc ttgttcacgt attggtttgt   2400

ctctatgttt gttatatgca ctaagaactt tatctaaatt ggcatctgct aaaataacac   2460

gcttagaaaa ttcactgatt tgctcaataa tctcatctaa ataatgctta tgctgctcca   2520

caaacaattg tttttgttcg ttatcttctg gactaccctt caacttttca taatgactag   2580

ctaaatataa aaaattcaca tatttgcttg gcagagccag ctcatttcct ttttgtaatt   2640

ctccggcact agccagcatc cgtttacgac cgttttctaa ctcaaaaaga ctatatttag   2700

gtagtttaat gattaagtct tttttaactt ccttatatcc tttagcttct aaaaagtcaa   2760

tcggattttt ttcaaaggaa cttctttcca taattgtgat ccctagtaac tctttaacgg   2820

attttaactt cttcgatttc cctttttcca ccttagcaac cactaggact gaataagcta   2880

ccgttggact atcaaaacca ccatattttt ttggatccca gtctttttta cgagcaataa   2940

gcttgtccga atttcttttt ggtaaaattg actccttgga gaatccgcct gtctgtactt   3000

ctgttttctt gacaatattg acttggggca tggacaatac tttgcgcact gtggcaaaat   3060

ctcgcccttt atcccagaca atttctccag tttccccatt agtttcgatt agagggcgtt   3120

tgcgaatctc tccatttgca agtgtaattt ctgttttgaa gaagttcatg atattagagt   3180

aaaagaaata ttttgcggtt gctttgccta tttcttgctc agacttagca atcattttac   3240

gaacatcata aactttataa tcaccataga caaactccga ttcaagtttt ggatatttct   3300

taatcaaagc agttccaacg acggcattta gatacgcatc atgggcatga tggtaattgt   3360

taatctcacg tactttatag aattggaaat cttttcggaa gtcagaaact aatttagatt   3420

ttaaggtaat cactttaacc tctcgaataa gtttatcatt ttcatcgtat ttagtattca   3480

tgcgactatc caaaatttgt gccacatgct tagtgatttg gcgagtttca accaattggc   3540

gtttgataaa accagcttta tcaagttcac tcaaacctcc acgttcagct ttcgttaaat   3600

tatcaaactt acgttgagtg attaacttgg cgtttagaag ttgtctccaa tagtttttca   3660

tctttttgac tacttcttca cttggaacgt tatccgattt accacgattt ttatcagaac   3720

gcgttaagac cttattgtct attgaatcgt ctttaaggaa actttgtgga acaatggcat   3780

cgacatcata atcacttaaa cgattaatat ctaattcttg gtccacatac atgtctcttc   3840

cattttggag ataatagaga tagagctttt cattttgcaa ttgagtattt tcaacaggat   3900

gctctttaag aatctgactt cctaattctt tgataccttc ttcgattcgt ttcatacgct   3960

ctcgcgaatt tttctggccc ttttgagttg tctgattttc acgtgccatt tcaataacga   4020

tattttctgg cttatgccgc cccattactt tgaccaattc atcaacaact tttacagtct   4080

gtaaaatacc ttttttaata gcagggctac cagctaaatt tgcaatatgt tcatgtaaac   4140

tatcgccttg tccagacact tgtgcttttt gaatgtcttc tttaaatgtc aaactatcat   4200

catggatcag ctgcataaaa ttgcgattgg caaaaccatc tgatttcaaa aaatctaata   4260

ttgttttgcc agattgctta tccctaatac cattaatcaa ttttcgagac aaacgtcccc   4320

aaccagtata acggcgacgt ttaagctgtt tcatcacctt atcatcaaag aggtgagcat   4380

atgttttaag tctttcctca atcatctccc tatcttcaaa taaggtcaat gttaaaacaa   4440

tatcctctaa gatatcttca ttttcttcat tatccaaaaa atctttatct ttaataattt   4500

ttagcaaatc atggtaggta cctaatgaag cattaaatct atcttcaact cctgaaattt   4560

caacactatc aaaacattct atttttttga aataatcttc ttttaattgc ttaacggtta   4620

cttttcgatt tgttttgaag agtaaatcaa caatggcttt cttctgttca cctgaaagaa   4680

atgctggttt tcgcattcct tcagtaacat atttgacctt tgtcaattcg ttataaaccg   4740

taaaatactc ataaagcaaa ctatgttttg gtagtacttt ttcatttgga agatttttat   4800

caaagtttgt catgcgttca ataaatgatt gagctgaagc acctttatcg acaacttctt   4860

caaaattcca tggggtaatt gtttcttcag acttccgagt catccatgca aaacgactat   4920

tgccacgcgc caatggacca acataataag gaattcgaaa agtcaagatt ttttcaatct   4980

tctcacgatt gtcttttaaa aatggataaa agtcttcttg tcttctcaaa atagcatgca   5040

gctcacccaa gtgaatttga tggggaatag agccgttgtc aaaggtccgt tgcttgcgca   5100

gcaaatcttc acgatttagt ttcaccaata attcctcagt accatccatt ttttctaaaa   5160

ttggtttgat aaatttataa aattcttctt ggctagctcc cccatcaata taacctgcat   5220

atccgttttt tgattgatca aaaaagattt ctttatactt ttctggaagt tgttgtcgaa   5280

ctaaagcttt taaaagagtc aagtcttgat gatgttcatc gtagcgttta atcattgaag   5340

ctgatagggg agccttagtt atttcagtat ttactcttag gatatctgaa agtaaaatag   5400

catctgataa attcttagct gccaaaaaca aatcagcata ttgatctcca atttgcgcca   5460

ataaattatc taaatcatca tcgtaagtat cttttgaaag ctgtaattta gcatcttctg   5520

ccaaatcaaa atttgattta aaattagggg tcaaacccaa tgacaaagca atgagattcc   5580

caaataagcc atttttcttc tcaccgggga gctgagcaat gagattttct aatcgtcttg   5640

atttactcaa tcgtgcagaa agaatcgctt tagcatctac tccacttgcg ttaatagggt   5700

tttcttcaaa taattgattg taggtttgta ccaactggat aaatagtttg tccacatcac   5760

tattatcagg atttaaatct ccctcaatca aaaaatgacc acgaaactta atcatatgcg   5820

ctaaggccaa atagattaag cgcaaatccg ctttatcagt agaatctacc aatttttttc   5880

gcagatgata gatagttgga tatttctcat gataagcaac ttcatctact atatttccaa   5940

aaataggatg acgttcatgc ttcttgtctt cttccaccaa aaaagactct tcaagtcgat   6000

gaaagaaact atcatctact ttcgccatct catttgaaaa aatctcctgt agataacaaa   6060

tacgattctt ccgacgtgta taccttctac gagctgtccg tttgagacga gtcgcttccg   6120

ctgtctctcc actgtcaaat aaaagagccc ctataagatt ttttttgata ctgtggcggt   6180

ctgtatttcc cagaaccttg aactttttag acggaacctt atattcatca gtgatcaccg   6240

cccatccgac gctatttgtg ccgatagcta agcctattga gtatttctta tccatagatc   6300

ctttctcctc tttagatctg ctagcataat acctagggct gagctagccg taaatgaggt   6360

ttcagcaaaa aacccctcaa gacccgttta gaggccccaa ggggttatgc tagttattgc   6420

tcagcggatt aattattaga aaaattcatc cagcatcaga tgaaattgca gtttgttcat   6480

atccggatta tcaatgccat atttctgaaa cagacgtttt tgcaggctcg ggctaaattc   6540

gcccaggcag ttccacagaa tggccagatc ctgataacga tccgcaatgc ccacacggcc   6600

cacatcaatg cagccaatca gtttgccttc atcgaaaatc aggttatcca ggctaaaatc   6660

gccgtgggtc accacgctat ccgggctaaa cggcagcagt ttatgcattt ctttccacac   6720

ctgttccacc ggccagccgt tacgttcatc atcaaaatcg ctcgcatcca ccaggccgtt   6780

gttcatacgg ctctgcgcct gggccagacg aaacacacga tcgctgttaa acgggcagtt   6840

gcacaccgga atgctatgca gacgacgcag aaacacggcc agcgcatcca caatgttttc   6900

gccgctatcc ggatattctt ccagcacctg aaacgcggtt ttgcccggaa tcgcggtggt   6960

cagcagccac gcatcatccg gggtgcgaat aaaatgttta atggtcggca gcggcataaa   7020

ttcggtcagc cagttcagac gcaccatttc atcggtcaca tcgttcgcca cgctgccttt   7080

gccatgtttc agaaacagtt ccggcgcatc cggtttgcca tacagacgat aaatggtcgc   7140

gccgctctga cccacgttat cacgcgccca tttatagcca tacagatccg catccatgtt   7200

gctgttcaga cgcggacggc tacagctcgt ttcacgctga atatggctca taacacccct   7260

tgtattactg tttatgtaag cagacagttt tattgttcat gatgatatat ttttatcttg   7320

tgcaatgtaa catcagagat tttgagacac aaatttaaat cgtaattatt ggggacccct   7380

ggattctcac caataaaaaa cgcccggcgg caaccgagcg ttctgaacaa atccagatgg   7440

agttctgagg tcattactgg atctatcaac aggagtccaa gactagtcgc cagggttttc   7500

ccagtcacga cgcggccgca agcttgcatg cctgcaggtc gactctagag gatccccggg   7560

taccgagctc gaattcgcgc ggccgcggcc taggcggcct cctgtgtgaa attgttatcc   7620

gctttaatta a                                                        7631


