                         SEQUENCE LISTING

<110>  Helmholtz Zentrum Muenchen GmbH
 
<120>  TREATMENT OF DISEASES CAUSED BY FRAME SHIFT MUTATIONS

<130>  HEL16679PCT

<150>  LU 101423
<151>  2019-10-02

<160>  34    

<170>  PatentIn version 3.5

<210>  1
<211>  1368
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cas9 from S. pyogenes

<400>  1

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  2
<211>  573
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N-split-Cas9-v1 (split between 573 and 574)

<400>  2

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 
                565                 570             


<210>  3
<211>  637
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N-split-Cas9-v2 (split between 637 and 638)

<400>  3

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 
625                 630                 635         


<210>  4
<211>  795
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-split-Cas9-v1 (split between 573 and 574)

<400>  4

Cys Phe Asp Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala 
1               5                   10                  15      


Ser Leu Gly Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp 
            20                  25                  30          


Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu 
        35                  40                  45              


Thr Leu Thr Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys 
    50                  55                  60                  


Thr Tyr Ala His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg 
65                  70                  75                  80  


Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly 
                85                  90                  95      


Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser 
            100                 105                 110         


Asp Gly Phe Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser 
        115                 120                 125             


Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly 
    130                 135                 140                 


Asp Ser Leu His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile 
145                 150                 155                 160 


Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys 
                165                 170                 175     


Val Met Gly Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg 
            180                 185                 190         


Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met 
        195                 200                 205             


Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys 
    210                 215                 220                 


Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu 
225                 230                 235                 240 


Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp 
                245                 250                 255     


Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser 
            260                 265                 270         


Phe Leu Lys Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp 
        275                 280                 285             


Lys Asn Arg Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys 
    290                 295                 300                 


Lys Met Lys Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr 
305                 310                 315                 320 


Gln Arg Lys Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser 
                325                 330                 335     


Glu Leu Asp Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg 
            340                 345                 350         


Gln Ile Thr Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr 
        355                 360                 365             


Lys Tyr Asp Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr 
    370                 375                 380                 


Leu Lys Ser Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr 
385                 390                 395                 400 


Lys Val Arg Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu 
                405                 410                 415     


Asn Ala Val Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu Glu 
            420                 425                 430         


Ser Glu Phe Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg Lys Met 
        435                 440                 445             


Ile Ala Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr Ala Lys Tyr Phe 
    450                 455                 460                 


Phe Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu Ile Thr Leu Ala 
465                 470                 475                 480 


Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu Thr Asn Gly Glu Thr 
                485                 490                 495     


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


Val Leu Ser Met Pro Gln Val Asn Ile Val Lys Lys Thr Glu Val Gln 
        515                 520                 525             


Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro Lys Arg Asn Ser Asp 
    530                 535                 540                 


Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro Lys Lys Tyr Gly Gly 
545                 550                 555                 560 


Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu Val Val Ala Lys Val 
                565                 570                 575     


Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val Lys Glu Leu Leu Gly 
            580                 585                 590         


Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys Asn Pro Ile Asp Phe 
        595                 600                 605             


Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys Asp Leu Ile Ile Lys 
    610                 615                 620                 


Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn Gly Arg Lys Arg Met 
625                 630                 635                 640 


Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro 
                645                 650                 655     


Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys Leu 
            660                 665                 670         


Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val Glu Gln 
        675                 680                 685             


His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser Glu Phe Ser 
    690                 695                 700                 


Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys Val Leu Ser Ala 
705                 710                 715                 720 


Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu Gln Ala Glu Asn Ile 
                725                 730                 735     


Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala Pro Ala Ala Phe Lys 
            740                 745                 750         


Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr Thr Ser Thr Lys Glu 
        755                 760                 765             


Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile Thr Gly Leu Tyr Glu 
    770                 775                 780                 


Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 
785                 790                 795 


<210>  5
<211>  731
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-split-Cas9-v2 (split between 637 and 638)

<400>  5

Thr Tyr Ala His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg 
1               5                   10                  15      


Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly 
            20                  25                  30          


Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser 
        35                  40                  45              


Asp Gly Phe Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser 
    50                  55                  60                  


Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly 
65                  70                  75                  80  


Asp Ser Leu His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile 
                85                  90                  95      


Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys 
            100                 105                 110         


Val Met Gly Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg 
        115                 120                 125             


Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met 
    130                 135                 140                 


Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys 
145                 150                 155                 160 


Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu 
                165                 170                 175     


Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp 
            180                 185                 190         


Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser 
        195                 200                 205             


Phe Leu Lys Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp 
    210                 215                 220                 


Lys Asn Arg Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys 
225                 230                 235                 240 


Lys Met Lys Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr 
                245                 250                 255     


Gln Arg Lys Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser 
            260                 265                 270         


Glu Leu Asp Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg 
        275                 280                 285             


Gln Ile Thr Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr 
    290                 295                 300                 


Lys Tyr Asp Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr 
305                 310                 315                 320 


Leu Lys Ser Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr 
                325                 330                 335     


Lys Val Arg Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu 
            340                 345                 350         


Asn Ala Val Val Gly Thr Ala Leu Ile Lys Lys Tyr Pro Lys Leu Glu 
        355                 360                 365             


Ser Glu Phe Val Tyr Gly Asp Tyr Lys Val Tyr Asp Val Arg Lys Met 
    370                 375                 380                 


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


Phe Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu Ile Thr Leu Ala 
                405                 410                 415     


Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu Thr Asn Gly Glu Thr 
            420                 425                 430         


Gly Glu Ile Val Trp Asp Lys Gly Arg Asp Phe Ala Thr Val Arg Lys 
        435                 440                 445             


Val Leu Ser Met Pro Gln Val Asn Ile Val Lys Lys Thr Glu Val Gln 
    450                 455                 460                 


Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro Lys Arg Asn Ser Asp 
465                 470                 475                 480 


Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro Lys Lys Tyr Gly Gly 
                485                 490                 495     


Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu Val Val Ala Lys Val 
            500                 505                 510         


Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val Lys Glu Leu Leu Gly 
        515                 520                 525             


Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys Asn Pro Ile Asp Phe 
    530                 535                 540                 


Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys Asp Leu Ile Ile Lys 
545                 550                 555                 560 


Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn Gly Arg Lys Arg Met 
                565                 570                 575     


Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn Glu Leu Ala Leu Pro 
            580                 585                 590         


Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser His Tyr Glu Lys Leu 
        595                 600                 605             


Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln Leu Phe Val Glu Gln 
    610                 615                 620                 


His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln Ile Ser Glu Phe Ser 
625                 630                 635                 640 


Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys Val Leu Ser Ala 
                645                 650                 655     


Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu Gln Ala Glu Asn Ile 
            660                 665                 670         


Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala Pro Ala Ala Phe Lys 
        675                 680                 685             


Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr Thr Ser Thr Lys Glu 
    690                 695                 700                 


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


Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 
                725                 730     


<210>  6
<211>  138
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Intein from N. punctiforme

<400>  6

Cys Leu Ser Tyr Glu Thr Glu Ile Leu Thr Val Glu Tyr Gly Leu Leu 
1               5                   10                  15      


Pro Ile Gly Lys Ile Val Glu Lys Arg Ile Glu Cys Thr Val Tyr Ser 
            20                  25                  30          


Val Asp Asn Asn Gly Asn Ile Tyr Thr Gln Pro Val Ala Gln Trp His 
        35                  40                  45              


Asp Arg Gly Glu Gln Glu Val Phe Glu Tyr Cys Leu Glu Asp Gly Ser 
    50                  55                  60                  


Leu Ile Arg Ala Thr Lys Asp His Lys Phe Met Thr Val Asp Gly Gln 
65                  70                  75                  80  


Met Leu Pro Ile Asp Glu Ile Phe Glu Arg Glu Leu Asp Leu Met Arg 
                85                  90                  95      


Val Asp Asn Leu Pro Asn Met Ile Lys Ile Ala Thr Arg Lys Tyr Leu 
            100                 105                 110         


Gly Lys Gln Asn Val Tyr Asp Ile Gly Val Glu Arg Asp His Asn Phe 
        115                 120                 125             


Ala Leu Lys Asn Gly Phe Ile Ala Ser Asn 
    130                 135             


<210>  7
<211>  145
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  NrdJ-1 Intein

<400>  7

Cys Leu Val Gly Ser Ser Glu Ile Ile Thr Arg Asn Tyr Gly Lys Thr 
1               5                   10                  15      


Thr Ile Lys Glu Val Val Glu Ile Phe Asp Asn Asp Lys Asn Ile Gln 
            20                  25                  30          


Val Leu Ala Phe Asn Thr His Thr Asp Asn Ile Glu Trp Ala Pro Ile 
        35                  40                  45              


Lys Ala Ala Gln Leu Thr Arg Pro Asn Ala Glu Leu Val Glu Leu Glu 
    50                  55                  60                  


Ile Asp Thr Leu His Gly Val Lys Thr Ile Arg Cys Thr Pro Asp His 
65                  70                  75                  80  


Pro Val Tyr Thr Lys Asn Arg Gly Tyr Val Arg Ala Asp Glu Leu Thr 
                85                  90                  95      


Asp Asp Asp Glu Leu Val Val Ala Ile Met Glu Ala Lys Thr Tyr Ile 
            100                 105                 110         


Gly Lys Leu Lys Ser Arg Lys Ile Val Ser Asn Glu Asp Thr Tyr Asp 
        115                 120                 125             


Ile Gln Thr Ser Thr His Asn Phe Phe Ala Asn Asp Ile Leu Val His 
    130                 135                 140                 


Asn 
145 


<210>  8
<211>  125
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Gp41-1 Intein

<400>  8

Cys Leu Asp Leu Lys Thr Gln Val Gln Thr Pro Gln Gly Met Lys Glu 
1               5                   10                  15      


Ile Ser Asn Ile Gln Val Gly Asp Leu Val Leu Ser Asn Thr Gly Tyr 
            20                  25                  30          


Asn Glu Val Leu Asn Val Phe Pro Lys Ser Lys Lys Lys Ser Tyr Lys 
        35                  40                  45              


Ile Thr Leu Glu Asp Gly Lys Glu Ile Ile Cys Ser Glu Glu His Leu 
    50                  55                  60                  


Phe Pro Thr Gln Thr Gly Glu Met Asn Ile Ser Gly Gly Leu Lys Glu 
65                  70                  75                  80  


Gly Met Cys Leu Tyr Val Lys Glu Met Met Leu Lys Lys Ile Leu Lys 
                85                  90                  95      


Ile Glu Glu Leu Asp Glu Arg Glu Leu Ile Asp Ile Glu Val Ser Gly 
            100                 105                 110         


Asn His Leu Phe Tyr Ala Asn Asp Ile Leu Thr His Asn 
        115                 120                 125 


<210>  9
<211>  102
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N-terminal splicing region of N. punctiforme

<400>  9

Cys Leu Ser Tyr Glu Thr Glu Ile Leu Thr Val Glu Tyr Gly Leu Leu 
1               5                   10                  15      


Pro Ile Gly Lys Ile Val Glu Lys Arg Ile Glu Cys Thr Val Tyr Ser 
            20                  25                  30          


Val Asp Asn Asn Gly Asn Ile Tyr Thr Gln Pro Val Ala Gln Trp His 
        35                  40                  45              


Asp Arg Gly Glu Gln Glu Val Phe Glu Tyr Cys Leu Glu Asp Gly Ser 
    50                  55                  60                  


Leu Ile Arg Ala Thr Lys Asp His Lys Phe Met Thr Val Asp Gly Gln 
65                  70                  75                  80  


Met Leu Pro Ile Asp Glu Ile Phe Glu Arg Glu Leu Asp Leu Met Arg 
                85                  90                  95      


Val Asp Asn Leu Pro Asn 
            100         


<210>  10
<211>  105
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N-terminal splicing region of NrdJ-1

<400>  10

Cys Leu Val Gly Ser Ser Glu Ile Ile Thr Arg Asn Tyr Gly Lys Thr 
1               5                   10                  15      


Thr Ile Lys Glu Val Val Glu Ile Phe Asp Asn Asp Lys Asn Ile Gln 
            20                  25                  30          


Val Leu Ala Phe Asn Thr His Thr Asp Asn Ile Glu Trp Ala Pro Ile 
        35                  40                  45              


Lys Ala Ala Gln Leu Thr Arg Pro Asn Ala Glu Leu Val Glu Leu Glu 
    50                  55                  60                  


Ile Asp Thr Leu His Gly Val Lys Thr Ile Arg Cys Thr Pro Asp His 
65                  70                  75                  80  


Pro Val Tyr Thr Lys Asn Arg Gly Tyr Val Arg Ala Asp Glu Leu Thr 
                85                  90                  95      


Asp Asp Asp Glu Leu Val Val Ala Ile 
            100                 105 


<210>  11
<211>  88
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N-terminal splicing region of gp41-1

<400>  11

Cys Leu Asp Leu Lys Thr Gln Val Gln Thr Pro Gln Gly Met Lys Glu 
1               5                   10                  15      


Ile Ser Asn Ile Gln Val Gly Asp Leu Val Leu Ser Asn Thr Gly Tyr 
            20                  25                  30          


Asn Glu Val Leu Asn Val Phe Pro Lys Ser Lys Lys Lys Ser Tyr Lys 
        35                  40                  45              


Ile Thr Leu Glu Asp Gly Lys Glu Ile Ile Cys Ser Glu Glu His Leu 
    50                  55                  60                  


Phe Pro Thr Gln Thr Gly Glu Met Asn Ile Ser Gly Gly Leu Lys Glu 
65                  70                  75                  80  


Gly Met Cys Leu Tyr Val Lys Glu 
                85              


<210>  12
<211>  36
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-terminal splicing region of N. punctiforme

<400>  12

Met Ile Lys Ile Ala Thr Arg Lys Tyr Leu Gly Lys Gln Asn Val Tyr 
1               5                   10                  15      


Asp Ile Gly Val Glu Arg Asp His Asn Phe Ala Leu Lys Asn Gly Phe 
            20                  25                  30          


Ile Ala Ser Asn 
        35      


<210>  13
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-terminal splicing region of NrdJ-1

<400>  13

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


Ser Asn Glu Asp Thr Tyr Asp Ile Gln Thr Ser Thr His Asn Phe Phe 
            20                  25                  30          


Ala Asn Asp Ile Leu Val His Asn 
        35                  40  


<210>  14
<211>  37
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  C-terminal splicing region of g41-1

<400>  14

Met Met Leu Lys Lys Ile Leu Lys Ile Glu Glu Leu Asp Glu Arg Glu 
1               5                   10                  15      


Leu Ile Asp Ile Glu Val Ser Gly Asn His Leu Phe Tyr Ala Asn Asp 
            20                  25                  30          


Ile Leu Thr His Asn 
        35          


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

<220>
<223>  SV40 NLS

<400>  15

Pro Lys Lys Lys Arg Lys Val 
1               5           


<210>  16
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2xSV40 NLS

<400>  16

Pro Lys Lys Lys Arg Lys Val Glu Asp Pro Lys Lys Lys Arg Lys Val 
1               5                   10                  15      


Asp 
    


<210>  17
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nucleoplasmin NLS

<400>  17

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


Lys Lys Leu Asp 
            20  


<210>  18
<211>  25
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  MSRRRKANPTKLSENAKKLAKEVEN

<400>  18

Met Ser Arg Arg Arg Lys Ala Asn Pro Thr Lys Leu Ser Glu Asn Ala 
1               5                   10                  15      


Lys Lys Leu Ala Lys Glu Val Glu Asn 
            20                  25  


<210>  19
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  c-Myc NLS

<400>  19

Pro Ala Ala Lys Arg Val Lys Leu Asp 
1               5                   


<210>  20
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TUS protein NLS

<400>  20

Lys Leu Lys Ile Lys Arg Pro Val Lys 
1               5                   


<210>  21
<211>  257
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  U6 promoter

<400>  21
aaggtcgggc aggaagaggg cctatttccc atgattcctt catatttgca tatacgatac       60

aaggctgtta gagagataat tagaattaat ttgactgtaa acacaaagat attagtacaa      120

aatacgtgac gtagaaagta ataatttctt gggtagtttg cagttttaaa attatgtttt      180

aaaatggact atcatatgct taccgtaact tgaaagtatt tcgatttctt ggctttatat      240

atcttgtgga aaggacg                                                     257


<210>  22
<211>  799
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CHB promoter

<400>  22
cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt       60

gacgtcaata gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg      120

gtaaactgcc cacttggcag tacatcaagt gtatcatatg ccaagtacgc cccctattga      180

cgtcaatgac ggtaaatggc ccgcctggca ttgtgcccag tacatgacct tatgggactt      240

tcctacttgg cagtacatct acgtattagt catcgctatt accatggtcg aggtgagccc      300

cacgttctgc ttcactctcc ccatctcccc cccctcccca cccccaattt tgtatttatt      360

tattttttaa ttattttgtg cagcgatggg ggcggggggg gggggggggc gcgcgccagg      420

cggggcgggg cggggcgagg ggcggggcgg ggcgaggcgg agaggtgcgg cggcagccaa      480

tcagagcggc gcgctccgaa agtttccttt tatggcgagg cggcggcggc ggcggcccta      540

taaaaagcga agcgcgcggc gggcgggagt cgctgcgacg ctgccttcgc cccgtgcccc      600

gctccgccgc cgcctcgcgc cgcccgcccc ggctctgact gaccgcgtta ctcccacagg      660

tgagcgggcg ggacggccct tctcctccgg gctgtaatta gctgagcaag aggtaagggt      720

ttaagggatg gttggttggt ggggtattaa tgtttaatta cctggagcac ctgcctgaaa      780

tcactttttt tcaggttgg                                                   799


<210>  23
<211>  1095
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Human exon 51 of DMD

<400>  23
aacaggattg tctaccagac attttaattc tagtactatg catcttaacc attaccatag       60

gctgacttac tctacagtgt ccaacactat tcatattaag atttatttaa tgactttgaa      120

acagtatttc atgtctaaat agaaaaacta ctaactcgca tttttaagaa aatattgtat      180

cttggttttt cttcactgct ggccagttta ctaacaatct gaaataaaaa gaaaaaaata      240

tgataaactg ctcccagtat aaaatacaga gctaagacaa gaacgtttca ttggctttga      300

tttccctagg gtccagcttc aaattaattt acttcctatt caagggaatt ttaaatcaga      360

aagaagatct tatcccatct tgttttgcct ttgttttttc ttgaataaaa aaaaaataag      420

taaaatttat ttccctggca aggtctgaaa acttttgttt tctttaccac ttccacaatg      480

tatatgattg ttactgagaa ggcttattta acttaagtta cttgtccagg catgagaatg      540

agcaaaatcg ttttttaaaa aattgttaaa tgtatattaa tgaaaaggtt gaatcttttc      600

attttctacc atgtattgct aaacaaagta tccacattgt tagaaaaaga tatataatgt      660

catgaataag agtttggctc aaattgttac tcttcaatta aatttgactt attgttattg      720

aaattggctc tttagcttgt gtttctaatt tttctttttc ttcttttttc ctttttgcaa      780

aaacccaaaa tattttagct cctactcaga ctgttactct ggtgacacaa cctgtggtta      840

ctaaggaaac tgccatctcc aaactagaaa tgccatcttc cttgatgttg gaggtacctg      900

ctctggcaga tttcaaccgg gcttggacag aacttaccga ctggctttct ctgcttgatc      960

aagttataaa atcacagagg gtgatggtgg gtgaccttga ggatatcaac gagatgatca     1020

tcaagcagaa ggtatgagaa aaaatgataa aagttggcag aagtttttct ttaaaatgaa     1080

gattttccac caatc                                                      1095


<210>  24
<211>  1029
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Porcine exon 51 DMD

<400>  24
gagaggaatt ctctgccagc tatttttact ctggaacttc aggtcttaac cattaccttg       60

tgttccctta caccacaatg ttcaacacta ttaacattaa tttaatattt cttaagagcc      120

ttgaaatggt gtctcattat ccaagtggaa aaactttact agctctgatt ttccaagaat      180

aatatagctt gggttttctt tactgctagc cactttatta tcagtctgaa agaaaaagaa      240

aaaaaatata taaactgcta ccaatataaa ataaagagca aaggcaagaa catttcattg      300

gttttgattt ccctagagtc cacttccaaa gcaatttacc tcttattcaa ggaaattgta      360

agtttgaaat aagatcttat ccaattttta cttttttccc cttgaacaaa aaaaaaagta      420

aaacattcac cttatcaaag tttgaatact ttatattttt ctttaccagt tcagcaactg      480

tataattgtt attgagggct ttttaggtta aattaattgc tcacctatag gaataatcaa      540

aatggttttg aaagattgtt aaatatgtat taatgaaaaa tttgaatctt tgaattattc      600

taccatgtag tactcatgtt tctaggagaa aaacatgtaa tgtcataaaa aatactttgg      660

ctcaaattgt tgccctttaa ttagttttat tgttattgaa actggcttct tagcttgtgt      720

ttctaatttt ccttttttct ttttcccttt ttgaaaaaaa aaatttagct actagtcaga      780

ctgttactct ggtgacacaa cccacagtta ccaaggaaac tgccatctcc aaaccagaaa      840

tgccatcttc cttgctgttg gaggtacctg ctctggcaga tttcaacagg gcttggacag      900

aacttaccga ctggctgtct ctgcttgatc gagttataaa atcacagagg gtgatggtgg      960

gtgatcttga agacatcaac gagatgatca tcaagcagaa ggtatggggg gaataaagat     1020

aagagctgg                                                             1029


<210>  25
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  first spacer sequence pig

<400>  25
gagagttcct aaggtagaga g                                                 21


<210>  26
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  first spacer sequence human

<400>  26
gataaagata agagctggca g                                                 21


<210>  27
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  second spacer sequence pig

<400>  27
gtaatttgaa gctggaccct a                                                 21


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

<220>
<223>  second spacer sequence human

<400>  28
gtctaggaga gtaaagtgat                                                   20


<210>  29
<211>  93
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  sgRNA backbone sequence

<400>  29
gtttaagagc tatgctggaa acagcatagc aagtttaaat aaggctagtc cgttatcaac       60

ttgaaaaagt ggcaccgagt cggtgctttt ttt                                    93


<210>  30
<211>  39
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Sequence from Fig. 11A

<400>  30
tagaacaaaa ggtgacaatc tgaatgtatt tgtgtgaaa                              39


<210>  31
<211>  40
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Sequence froom Fig. 11A

<400>  31
ctaaagtagc ctgctatgat aagttgaaaa agggtttgta                             40


<210>  32
<211>  40
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Sequence from Fig. 11A

<400>  32
tagaacaaaa ggtgacaaat aagttgaaaa agggtttgta                             40


<210>  33
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  oligonucleotide

<400>  33
taatttgaag ctggacccta                                                   20


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

<220>
<223>  oligonucleotide

<400>  34
gtctaggaga gtaaagtgat                                                   20


