                         б

<110>  йѧԺŴ뷢ѧо
 
<120>  ֲеķ

<130>  P2020TC1283

<160>  14    

<170>  PatentIn version 3.5

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

<220>
<223>  nCas9(H840A)

<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 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>  3
<211>  678
<212>  PRT
<213>  Artificial sequence

<220>
<223>  ҰM-MLV

<400>  3

Met Thr Leu Asn Ile Glu Asp Glu Tyr Arg Leu His Glu Thr Ser Lys 
1               5                   10                  15      


Glu Pro Asp Val Ser Leu Gly Ser Thr Trp Leu Ser Asp Phe Pro Gln 
            20                  25                  30          


Ala Trp Ala Glu Thr Gly Gly Met Gly Leu Ala Val Arg Gln Ala Pro 
        35                  40                  45              


Leu Ile Ile Pro Leu Lys Ala Thr Ser Thr Pro Val Ser Ile Lys Gln 
    50                  55                  60                  


Tyr Pro Met Ser Gln Glu Ala Arg Leu Gly Ile Lys Pro His Ile Gln 
65                  70                  75                  80  


Arg Leu Leu Asp Gln Gly Ile Leu Val Pro Cys Gln Ser Pro Trp Asn 
                85                  90                  95      


Thr Pro Leu Leu Pro Val Lys Lys Pro Gly Thr Asn Asp Tyr Arg Pro 
            100                 105                 110         


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


Thr Val Pro Asn Pro Tyr Asn Leu Leu Ser Gly Leu Pro Pro Ser His 
    130                 135                 140                 


Gln Trp Tyr Thr Val Leu Asp Leu Lys Asp Ala Phe Phe Cys Leu Arg 
145                 150                 155                 160 


Leu His Pro Thr Ser Gln Pro Leu Phe Ala Phe Glu Trp Arg Asp Pro 
                165                 170                 175     


Glu Met Gly Ile Ser Gly Gln Leu Thr Trp Thr Arg Leu Pro Gln Gly 
            180                 185                 190         


Phe Lys Asn Ser Pro Thr Leu Phe Asp Glu Ala Leu His Arg Asp Leu 
        195                 200                 205             


Ala Asp Phe Arg Ile Gln His Pro Asp Leu Ile Leu Leu Gln Tyr Val 
    210                 215                 220                 


Asp Asp Leu Leu Leu Ala Ala Thr Ser Glu Leu Asp Cys Gln Gln Gly 
225                 230                 235                 240 


Thr Arg Ala Leu Leu Gln Thr Leu Gly Asn Leu Gly Tyr Arg Ala Ser 
                245                 250                 255     


Ala Lys Lys Ala Gln Ile Cys Gln Lys Gln Val Lys Tyr Leu Gly Tyr 
            260                 265                 270         


Leu Leu Lys Glu Gly Gln Arg Trp Leu Thr Glu Ala Arg Lys Glu Thr 
        275                 280                 285             


Val Met Gly Gln Pro Thr Pro Lys Thr Pro Arg Gln Leu Arg Glu Phe 
    290                 295                 300                 


Leu Gly Thr Ala Gly Phe Cys Arg Leu Trp Ile Pro Gly Phe Ala Glu 
305                 310                 315                 320 


Met Ala Ala Pro Leu Tyr Pro Leu Thr Lys Thr Gly Thr Leu Phe Asn 
                325                 330                 335     


Trp Gly Pro Asp Gln Gln Lys Ala Tyr Gln Glu Ile Lys Gln Ala Leu 
            340                 345                 350         


Leu Thr Ala Pro Ala Leu Gly Leu Pro Asp Leu Thr Lys Pro Phe Glu 
        355                 360                 365             


Leu Phe Val Asp Glu Lys Gln Gly Tyr Ala Lys Gly Val Leu Thr Gln 
    370                 375                 380                 


Lys Leu Gly Pro Trp Arg Arg Pro Val Ala Tyr Leu Ser Lys Lys Leu 
385                 390                 395                 400 


Asp Pro Val Ala Ala Gly Trp Pro Pro Cys Leu Arg Met Val Ala Ala 
                405                 410                 415     


Ile Ala Val Leu Thr Lys Asp Ala Gly Lys Leu Thr Met Gly Gln Pro 
            420                 425                 430         


Leu Val Ile Leu Ala Pro His Ala Val Glu Ala Leu Val Lys Gln Pro 
        435                 440                 445             


Pro Asp Arg Trp Leu Ser Asn Ala Arg Met Thr His Tyr Gln Ala Leu 
    450                 455                 460                 


Leu Leu Asp Thr Asp Arg Val Gln Phe Gly Pro Val Val Ala Leu Asn 
465                 470                 475                 480 


Pro Ala Thr Leu Leu Pro Leu Pro Glu Glu Gly Leu Gln His Asn Cys 
                485                 490                 495     


Leu Asp Ile Leu Ala Glu Ala His Gly Thr Arg Pro Asp Leu Thr Asp 
            500                 505                 510         


Gln Pro Leu Pro Asp Ala Asp His Thr Trp Tyr Thr Asp Gly Ser Ser 
        515                 520                 525             


Leu Leu Gln Glu Gly Gln Arg Lys Ala Gly Ala Ala Val Thr Thr Glu 
    530                 535                 540                 


Thr Glu Val Ile Trp Ala Lys Ala Leu Pro Ala Gly Thr Ser Ala Gln 
545                 550                 555                 560 


Arg Ala Glu Leu Ile Ala Leu Thr Gln Ala Leu Lys Met Ala Glu Gly 
                565                 570                 575     


Lys Lys Leu Asn Val Tyr Thr Asp Ser Arg Tyr Ala Phe Ala Thr Ala 
            580                 585                 590         


His Ile His Gly Glu Ile Tyr Arg Arg Arg Gly Leu Leu Thr Ser Glu 
        595                 600                 605             


Gly Lys Glu Ile Lys Asn Lys Asp Glu Ile Leu Ala Leu Leu Lys Ala 
    610                 615                 620                 


Leu Phe Leu Pro Lys Arg Leu Ser Ile Ile His Cys Pro Gly His Gln 
625                 630                 635                 640 


Lys Gly His Ser Ala Glu Ala Arg Gly Asn Arg Met Ala Asp Gln Ala 
                645                 650                 655     


Ala Arg Lys Ala Ala Ile Thr Glu Thr Pro Asp Thr Ser Thr Leu Leu 
            660                 665                 670         


Ile Glu Asn Ser Ser Pro 
        675             


<210>  4
<211>  678
<212>  PRT
<213>  Artificial sequence

<220>
<223>  M-MLV

<400>  4

Met Thr Leu Asn Ile Glu Asp Glu Tyr Arg Leu His Glu Thr Ser Lys 
1               5                   10                  15      


Glu Pro Asp Val Ser Leu Gly Ser Thr Trp Leu Ser Asp Phe Pro Gln 
            20                  25                  30          


Ala Trp Ala Glu Thr Gly Gly Met Gly Leu Ala Val Arg Gln Ala Pro 
        35                  40                  45              


Leu Ile Ile Pro Leu Lys Ala Thr Ser Thr Pro Val Ser Ile Lys Gln 
    50                  55                  60                  


Tyr Pro Met Ser Gln Glu Ala Arg Leu Gly Ile Lys Pro His Ile Gln 
65                  70                  75                  80  


Arg Leu Leu Asp Gln Gly Ile Leu Val Pro Cys Gln Ser Pro Trp Asn 
                85                  90                  95      


Thr Pro Leu Leu Pro Val Lys Lys Pro Gly Thr Asn Asp Tyr Arg Pro 
            100                 105                 110         


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


Thr Val Pro Asn Pro Tyr Asn Leu Leu Ser Gly Leu Pro Pro Ser His 
    130                 135                 140                 


Gln Trp Tyr Thr Val Leu Asp Leu Lys Asp Ala Phe Phe Cys Leu Arg 
145                 150                 155                 160 


Leu His Pro Thr Ser Gln Pro Leu Phe Ala Phe Glu Trp Arg Asp Pro 
                165                 170                 175     


Glu Met Gly Ile Ser Gly Gln Leu Thr Trp Thr Arg Leu Pro Gln Gly 
            180                 185                 190         


Phe Lys Asn Ser Pro Thr Leu Phe Asn Glu Ala Leu His Arg Asp Leu 
        195                 200                 205             


Ala Asp Phe Arg Ile Gln His Pro Asp Leu Ile Leu Leu Gln Tyr Val 
    210                 215                 220                 


Asp Asp Leu Leu Leu Ala Ala Thr Ser Glu Leu Asp Cys Gln Gln Gly 
225                 230                 235                 240 


Thr Arg Ala Leu Leu Gln Thr Leu Gly Asn Leu Gly Tyr Arg Ala Ser 
                245                 250                 255     


Ala Lys Lys Ala Gln Ile Cys Gln Lys Gln Val Lys Tyr Leu Gly Tyr 
            260                 265                 270         


Leu Leu Lys Glu Gly Gln Arg Trp Leu Thr Glu Ala Arg Lys Glu Thr 
        275                 280                 285             


Val Met Gly Gln Pro Thr Pro Lys Thr Pro Arg Gln Leu Arg Glu Phe 
    290                 295                 300                 


Leu Gly Lys Ala Gly Phe Cys Arg Leu Phe Ile Pro Gly Phe Ala Glu 
305                 310                 315                 320 


Met Ala Ala Pro Leu Tyr Pro Leu Thr Lys Pro Gly Thr Leu Phe Asn 
                325                 330                 335     


Trp Gly Pro Asp Gln Gln Lys Ala Tyr Gln Glu Ile Lys Gln Ala Leu 
            340                 345                 350         


Leu Thr Ala Pro Ala Leu Gly Leu Pro Asp Leu Thr Lys Pro Phe Glu 
        355                 360                 365             


Leu Phe Val Asp Glu Lys Gln Gly Tyr Ala Lys Gly Val Leu Thr Gln 
    370                 375                 380                 


Lys Leu Gly Pro Trp Arg Arg Pro Val Ala Tyr Leu Ser Lys Lys Leu 
385                 390                 395                 400 


Asp Pro Val Ala Ala Gly Trp Pro Pro Cys Leu Arg Met Val Ala Ala 
                405                 410                 415     


Ile Ala Val Leu Thr Lys Asp Ala Gly Lys Leu Thr Met Gly Gln Pro 
            420                 425                 430         


Leu Val Ile Leu Ala Pro His Ala Val Glu Ala Leu Val Lys Gln Pro 
        435                 440                 445             


Pro Asp Arg Trp Leu Ser Asn Ala Arg Met Thr His Tyr Gln Ala Leu 
    450                 455                 460                 


Leu Leu Asp Thr Asp Arg Val Gln Phe Gly Pro Val Val Ala Leu Asn 
465                 470                 475                 480 


Pro Ala Thr Leu Leu Pro Leu Pro Glu Glu Gly Leu Gln His Asn Cys 
                485                 490                 495     


Leu Asp Ile Leu Ala Glu Ala His Gly Thr Arg Pro Asp Leu Thr Asp 
            500                 505                 510         


Gln Pro Leu Pro Asp Ala Asp His Thr Trp Tyr Thr Asp Gly Ser Ser 
        515                 520                 525             


Leu Leu Gln Glu Gly Gln Arg Lys Ala Gly Ala Ala Val Thr Thr Glu 
    530                 535                 540                 


Thr Glu Val Ile Trp Ala Lys Ala Leu Pro Ala Gly Thr Ser Ala Gln 
545                 550                 555                 560 


Arg Ala Glu Leu Ile Ala Leu Thr Gln Ala Leu Lys Met Ala Glu Gly 
                565                 570                 575     


Lys Lys Leu Asn Val Tyr Thr Asp Ser Arg Tyr Ala Phe Ala Thr Ala 
            580                 585                 590         


His Ile His Gly Glu Ile Tyr Arg Arg Arg Gly Trp Leu Thr Ser Glu 
        595                 600                 605             


Gly Lys Glu Ile Lys Asn Lys Asp Glu Ile Leu Ala Leu Leu Lys Ala 
    610                 615                 620                 


Leu Phe Leu Pro Lys Arg Leu Ser Ile Ile His Cys Pro Gly His Gln 
625                 630                 635                 640 


Lys Gly His Ser Ala Glu Ala Arg Gly Asn Arg Met Ala Asp Gln Ala 
                645                 650                 655     


Ala Arg Lys Ala Ala Ile Thr Glu Thr Pro Asp Thr Ser Thr Leu Leu 
            660                 665                 670         


Ile Glu Asn Ser Ser Pro 
        675             


<210>  5
<211>  683
<212>  PRT
<213>  Artificial sequence

<220>
<223>  CaMVת¼ø

<400>  5

Met Asp His Leu Leu Leu Lys Thr Gln Thr Gln Thr Glu Gln Val Met 
1               5                   10                  15      


Asn Val Thr Asn Pro Asn Ser Ile Tyr Ile Lys Gly Arg Leu Tyr Phe 
            20                  25                  30          


Lys Gly Tyr Lys Lys Ile Glu Leu His Cys Phe Val Asp Thr Gly Ala 
        35                  40                  45              


Ser Leu Cys Ile Ala Ser Lys Phe Val Ile Pro Glu Glu His Trp Val 
    50                  55                  60                  


Asn Ala Glu Arg Pro Ile Met Val Lys Ile Ala Asp Gly Ser Ser Ile 
65                  70                  75                  80  


Thr Ile Ser Lys Val Cys Lys Asp Ile Asp Leu Ile Ile Ala Gly Glu 
                85                  90                  95      


Ile Phe Arg Ile Pro Thr Val Tyr Gln Gln Glu Ser Gly Ile Asp Phe 
            100                 105                 110         


Ile Ile Gly Asn Asn Phe Cys Gln Leu Tyr Glu Pro Phe Ile Gln Phe 
        115                 120                 125             


Thr Asp Arg Val Ile Phe Thr Lys Asn Lys Ser Tyr Pro Val His Ile 
    130                 135                 140                 


Ala Lys Leu Thr Arg Ala Val Arg Val Gly Thr Glu Gly Phe Leu Glu 
145                 150                 155                 160 


Ser Met Lys Lys Arg Ser Lys Thr Gln Gln Pro Glu Pro Val Asn Ile 
                165                 170                 175     


Ser Thr Asn Lys Ile Glu Asn Pro Leu Glu Glu Ile Ala Ile Leu Ser 
            180                 185                 190         


Glu Gly Arg Arg Leu Ser Glu Glu Lys Leu Phe Ile Thr Gln Gln Arg 
        195                 200                 205             


Met Gln Lys Ile Glu Glu Leu Leu Glu Lys Val Cys Ser Glu Asn Pro 
    210                 215                 220                 


Leu Asp Pro Asn Lys Thr Lys Gln Trp Met Lys Ala Ser Ile Lys Leu 
225                 230                 235                 240 


Ser Asp Pro Ser Lys Ala Ile Lys Val Lys Pro Met Lys Tyr Ser Pro 
                245                 250                 255     


Met Asp Arg Glu Glu Phe Asp Lys Gln Ile Lys Glu Leu Leu Asp Leu 
            260                 265                 270         


Lys Val Ile Lys Pro Ser Lys Ser Pro His Met Ala Pro Ala Phe Leu 
        275                 280                 285             


Val Asn Asn Glu Ala Glu Lys Arg Arg Gly Lys Lys Arg Met Val Val 
    290                 295                 300                 


Asn Tyr Lys Ala Met Asn Lys Ala Thr Val Gly Asp Ala Tyr Asn Leu 
305                 310                 315                 320 


Pro Asn Lys Asp Glu Leu Leu Thr Leu Ile Arg Gly Lys Lys Ile Phe 
                325                 330                 335     


Ser Ser Phe Asp Cys Lys Ser Gly Phe Trp Gln Val Leu Leu Asp Gln 
            340                 345                 350         


Glu Ser Arg Pro Leu Thr Ala Phe Thr Cys Pro Gln Gly His Tyr Glu 
        355                 360                 365             


Trp Asn Val Val Pro Phe Gly Leu Lys Gln Ala Pro Ser Ile Phe Gln 
    370                 375                 380                 


Arg His Met Asp Glu Ala Phe Arg Val Phe Arg Lys Phe Cys Cys Val 
385                 390                 395                 400 


Tyr Val Asp Asp Ile Leu Val Phe Ser Asn Asn Glu Glu Asp His Leu 
                405                 410                 415     


Leu His Val Ala Met Ile Leu Gln Lys Cys Asn Gln His Gly Ile Ile 
            420                 425                 430         


Leu Ser Lys Lys Lys Ala Gln Leu Phe Lys Lys Lys Ile Asn Phe Leu 
        435                 440                 445             


Gly Leu Glu Ile Asp Glu Gly Thr His Lys Pro Gln Gly His Ile Leu 
    450                 455                 460                 


Glu His Ile Asn Lys Phe Pro Asp Thr Leu Glu Asp Lys Lys Gln Leu 
465                 470                 475                 480 


Gln Arg Phe Leu Gly Ile Leu Thr Tyr Ala Ser Asp Tyr Ile Pro Lys 
                485                 490                 495     


Leu Ala Gln Ile Arg Lys Pro Leu Gln Ala Lys Leu Lys Glu Asn Val 
            500                 505                 510         


Pro Trp Arg Trp Thr Lys Glu Asp Thr Leu Tyr Met Gln Lys Val Lys 
        515                 520                 525             


Lys Asn Leu Gln Gly Phe Pro Pro Leu His His Pro Leu Pro Glu Glu 
    530                 535                 540                 


Lys Leu Ile Ile Glu Thr Asp Ala Ser Asp Asp Tyr Trp Gly Gly Met 
545                 550                 555                 560 


Leu Lys Ala Ile Lys Ile Asn Glu Gly Thr Asn Thr Glu Leu Ile Cys 
                565                 570                 575     


Arg Tyr Ala Ser Gly Ser Phe Lys Ala Ala Glu Lys Asn Tyr His Ser 
            580                 585                 590         


Asn Asp Lys Glu Thr Leu Ala Val Ile Asn Thr Ile Lys Lys Phe Ser 
        595                 600                 605             


Ile Tyr Leu Thr Pro Val His Phe Leu Ile Arg Thr Asp Asn Thr His 
    610                 615                 620                 


Phe Lys Ser Phe Val Asn Leu Asn Tyr Lys Gly Asp Ser Lys Leu Gly 
625                 630                 635                 640 


Arg Asn Ile Arg Trp Gln Ala Trp Leu Ser His Tyr Ser Phe Asp Val 
                645                 650                 655     


Glu His Ile Lys Gly Thr Asp Asn His Phe Ala Asp Phe Leu Ser Arg 
            660                 665                 670         


Glu Phe Asn Lys Val Asn Ser Ser Gly Gly Ser 
        675                 680             


<210>  6
<211>  329
<212>  PRT
<213>  Artificial sequence

<220>
<223>  retronת¼ø

<400>  6

Met Gly Ile His Gly Val Pro Ala Ala Met Lys Ser Ala Glu Tyr Leu 
1               5                   10                  15      


Asn Thr Phe Arg Leu Arg Asn Leu Gly Leu Pro Val Met Asn Asn Leu 
            20                  25                  30          


His Asp Met Ser Lys Ala Thr Arg Ile Ser Val Glu Thr Leu Arg Leu 
        35                  40                  45              


Leu Ile Tyr Thr Ala Asp Phe Arg Tyr Arg Ile Tyr Thr Val Glu Lys 
    50                  55                  60                  


Lys Gly Pro Glu Lys Arg Met Arg Thr Ile Tyr Gln Pro Ser Arg Glu 
65                  70                  75                  80  


Leu Lys Ala Leu Gln Gly Trp Val Leu Arg Asn Ile Leu Asp Lys Leu 
                85                  90                  95      


Ser Ser Ser Pro Phe Ser Ile Gly Phe Glu Lys His Gln Ser Ile Leu 
            100                 105                 110         


Asn Asn Ala Thr Pro His Ile Gly Ala Asn Phe Ile Leu Asn Ile Asp 
        115                 120                 125             


Leu Glu Asp Phe Phe Pro Ser Leu Thr Ala Asn Lys Val Phe Gly Val 
    130                 135                 140                 


Phe His Ser Leu Gly Tyr Asn Arg Leu Ile Ser Ser Val Leu Thr Lys 
145                 150                 155                 160 


Ile Cys Cys Tyr Lys Asn Leu Leu Pro Gln Gly Ala Pro Ser Ser Pro 
                165                 170                 175     


Lys Leu Ala Asn Leu Ile Cys Ser Lys Leu Asp Tyr Arg Ile Gln Gly 
            180                 185                 190         


Tyr Ala Gly Ser Arg Gly Leu Ile Tyr Thr Arg Tyr Ala Asp Asp Leu 
        195                 200                 205             


Thr Leu Ser Ala Gln Ser Met Lys Lys Val Val Lys Ala Arg Asp Phe 
    210                 215                 220                 


Leu Phe Ser Ile Ile Pro Ser Glu Gly Leu Val Ile Asn Ser Lys Lys 
225                 230                 235                 240 


Thr Cys Ile Ser Gly Pro Arg Ser Gln Arg Lys Val Thr Gly Leu Val 
                245                 250                 255     


Ile Ser Gln Glu Lys Val Gly Ile Gly Arg Glu Lys Tyr Lys Glu Ile 
            260                 265                 270         


Arg Ala Lys Ile His His Ile Phe Cys Gly Lys Ser Ser Glu Ile Glu 
        275                 280                 285             


His Val Arg Gly Trp Leu Ser Phe Ile Leu Ser Val Asp Ser Lys Ser 
    290                 295                 300                 


His Arg Arg Leu Ile Thr Tyr Ile Ser Lys Leu Glu Lys Lys Tyr Gly 
305                 310                 315                 320 


Lys Asn Pro Leu Asn Lys Ala Lys Thr 
                325                 


<210>  7
<211>  32
<212>  PRT
<213>  Artificial sequence

<220>
<223>  32aa linker

<400>  7

Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Ser Glu Thr Pro Gly Thr 
1               5                   10                  15      


Ser Glu Ser Ala Thr Pro Glu Ser Ser Gly Gly Ser Ser Gly Gly Ser 
            20                  25                  30          


<210>  8
<211>  76
<212>  RNA
<213>  Artificial sequence

<220>
<223>  gRNA֧

<400>  8
guuuuagagc uagaaauagc aaguuaaaau aaggcuaguc cguuaucaac uugaaaaagu       60

ggcaccgagu cggugc                                                       76


<210>  9
<211>  6327
<212>  DNA
<213>  Artificial sequence

<220>
<223> ںϵnCas9(H840A)-M-MLVĻ

<400>  9
atgcctaaga aaaagagaaa agtggacaag aagtactcga tcggcctcga tattgggact       60

aactctgttg gctgggccgt gatcaccgac gagtacaagg tgccctcaaa gaagttcaag      120

gtcctgggca acaccgatcg gcattccatc aagaagaatc tcattggcgc tctcctgttc      180

gacagcggcg agacggctga ggctacgcgg ctcaagcgca ccgcccgcag gcggtacacg      240

cgcaggaaga atcgcatctg ctacctgcag gagattttct ccaacgagat ggcgaaggtt      300

gacgattctt tcttccacag gctggaggag tcattcctcg tggaggagga taagaagcac      360

gagcggcatc caatcttcgg caacattgtc gacgaggttg cctaccacga gaagtaccct      420

acgatctacc atctgcggaa gaagctcgtg gactccacag ataaggcgga cctccgcctg      480

atctacctcg ctctggccca catgattaag ttcaggggcc atttcctgat cgagggggat      540

ctcaacccgg acaatagcga tgttgacaag ctgttcatcc agctcgtgca gacgtacaac      600

cagctcttcg aggagaaccc cattaatgcg tcaggcgtcg acgcgaaggc tatcctgtcc      660

gctaggctct cgaagtctcg gcgcctcgag aacctgatcg cccagctgcc gggcgagaag      720

aagaacggcc tgttcgggaa tctcattgcg ctcagcctgg ggctcacgcc caacttcaag      780

tcgaatttcg atctcgctga ggacgccaag ctgcagctct ccaaggacac atacgacgat      840

gacctggata acctcctggc ccagatcggc gatcagtacg cggacctgtt cctcgctgcc      900

aagaatctgt cggacgccat cctcctgtct gatattctca gggtgaacac cgagattacg      960

aaggctccgc tctcagcctc catgatcaag cgctacgacg agcaccatca ggatctgacc     1020

ctcctgaagg cgctggtcag gcagcagctc cccgagaagt acaaggagat cttcttcgat     1080

cagtcgaaga acggctacgc tgggtacatt gacggcgggg cctctcagga ggagttctac     1140

aagttcatca agccgattct ggagaagatg gacggcacgg aggagctgct ggtgaagctc     1200

aatcgcgagg acctcctgag gaagcagcgg acattcgata acggcagcat cccacaccag     1260

attcatctcg gggagctgca cgctatcctg aggaggcagg aggacttcta ccctttcctc     1320

aaggataacc gcgagaagat cgagaagatt ctgactttca ggatcccgta ctacgtcggc     1380

ccactcgcta ggggcaactc ccgcttcgct tggatgaccc gcaagtcaga ggagacgatc     1440

acgccgtgga acttcgagga ggtggtcgac aagggcgcta gcgctcagtc gttcatcgag     1500

aggatgacga atttcgacaa gaacctgcca aatgagaagg tgctccctaa gcactcgctc     1560

ctgtacgagt acttcacagt ctacaacgag ctgactaagg tgaagtatgt gaccgagggc     1620

atgaggaagc cggctttcct gtctggggag cagaagaagg ccatcgtgga cctcctgttc     1680

aagaccaacc ggaaggtcac ggttaagcag ctcaaggagg actacttcaa gaagattgag     1740

tgcttcgatt cggtcgagat ctctggcgtt gaggaccgct tcaacgcctc cctggggacc     1800

taccacgatc tcctgaagat cattaaggat aaggacttcc tggacaacga ggagaatgag     1860

gatatcctcg aggacattgt gctgacactc actctgttcg aggaccggga gatgatcgag     1920

gagcgcctga agacttacgc ccatctcttc gatgacaagg tcatgaagca gctcaagagg     1980

aggaggtaca ccggctgggg gaggctgagc aggaagctca tcaacggcat tcgggacaag     2040

cagtccggga agacgatcct cgacttcctg aagagcgatg gcttcgcgaa ccgcaatttc     2100

atgcagctga ttcacgatga cagcctcaca ttcaaggagg atatccagaa ggctcaggtg     2160

agcggccagg gggactcgct gcacgagcat atcgcgaacc tcgctggctc gccagctatc     2220

aagaagggga ttctgcagac cgtgaaggtt gtggacgagc tggtgaaggt catgggcagg     2280

cacaagcctg agaacatcgt cattgagatg gcccgggaga atcagaccac gcagaagggc     2340

cagaagaact cacgcgagag gatgaagagg atcgaggagg gcattaagga gctggggtcc     2400

cagatcctca aggagcaccc ggtggagaac acgcagctgc agaatgagaa gctctacctg     2460

tactacctcc agaatggccg cgatatgtat gtggaccagg agctggatat taacaggctc     2520

agcgattacg acgtcgatgc catcgttcca cagtcattcc tgaaggatga ctccattgac     2580

aacaaggtcc tcaccaggtc ggacaagaac cggggcaagt ctgataatgt tccttcagag     2640

gaggtcgtta agaagatgaa gaactactgg cgccagctcc tgaatgccaa gctgatcacg     2700

cagcggaagt tcgataacct cacaaaggct gagaggggcg ggctctctga gctggacaag     2760

gcgggcttca tcaagaggca gctggtcgag acacggcaga tcactaagca cgttgcgcag     2820

attctcgact cacggatgaa cactaagtac gatgagaatg acaagctgat ccgcgaggtg     2880

aaggtcatca ccctgaagtc aaagctcgtc tccgacttca ggaaggattt ccagttctac     2940

aaggttcggg agatcaacaa ttaccaccat gcccatgacg cgtacctgaa cgcggtggtc     3000

ggcacagctc tgatcaagaa gtacccaaag ctcgagagcg agttcgtgta cggggactac     3060

aaggtttacg atgtgaggaa gatgatcgcc aagtcggagc aggagattgg caaggctacc     3120

gccaagtact tcttctactc taacattatg aatttcttca agacagagat cactctggcc     3180

aatggcgaga tccggaagcg ccccctcatc gagacgaacg gcgagacggg ggagatcgtg     3240

tgggacaagg gcagggattt cgcgaccgtc aggaaggttc tctccatgcc acaagtgaat     3300

atcgtcaaga agacagaggt ccagactggc gggttctcta aggagtcaat tctgcctaag     3360

cggaacagcg acaagctcat cgcccgcaag aaggactggg atccgaagaa gtacggcggg     3420

ttcgacagcc ccactgtggc ctactcggtc ctggttgtgg cgaaggttga gaagggcaag     3480

tccaagaagc tcaagagcgt gaaggagctg ctggggatca cgattatgga gcgctccagc     3540

ttcgagaaga acccgatcga tttcctggag gcgaagggct acaaggaggt gaagaaggac     3600

ctgatcatta agctccccaa gtactcactc ttcgagctgg agaacggcag gaagcggatg     3660

ctggcttccg ctggcgagct gcagaagggg aacgagctgg ctctgccgtc caagtatgtg     3720

aacttcctct acctggcctc ccactacgag aagctcaagg gcagccccga ggacaacgag     3780

cagaagcagc tgttcgtcga gcagcacaag cattacctcg acgagatcat tgagcagatt     3840

tccgagttct ccaagcgcgt gatcctggcc gacgcgaatc tggataaggt cctctccgcg     3900

tacaacaagc accgcgacaa gccaatcagg gagcaggctg agaatatcat tcatctcttc     3960

accctgacga acctcggcgc ccctgctgct ttcaagtact tcgacacaac tatcgatcgc     4020

aagaggtaca caagcactaa ggaggtcctg gacgcgaccc tcatccacca gtcgattacc     4080

ggcctctacg agacgcgcat cgacctgtct cagctcgggg gcgacgaatt cccaaagaag     4140

aagcggaagg tggagctcag cggaggatct tccggaggat ctagcggctc cgagacacca     4200

ggaacatccg aaagcgctac accagaatct agcggaggct cttccggagg atctaggcct     4260

accctcaaca tcgaggatga gtatcgcctc cacgaaacct ccaaagaacc ggacgtgtcc     4320

ctcggcagca catggctcag cgacttccca caagcgtggg ccgaaaccgg cggcatgggc     4380

ctcgccgtcc gccaagcccc actcattatc ccgctgaagg cgacctccac accggtgtcc     4440

atcaagcagt acccgatgag ccaagaggcg aggctcggga ttaagccgca cattcagcgc     4500

ctcctcgatc aaggcattct cgtgccgtgc caatccccgt ggaatacacc actcctcccg     4560

gtcaaaaagc cgggcaccaa cgactatcgc ccggtccaag atctccgcga ggtcaacaag     4620

cgcgtggaag acatccaccc gaccgtcccg aacccgtata atctgctctc cgggctccca     4680

ccatcccacc agtggtatac agtgctggac ctcaaagacg ccttcttctg tctccgcctc     4740

cacccaacaa gccagccgct cttcgccttc gagtggcgcg acccggagat gggcatctcc     4800

ggccaactga catggacacg cctcccgcaa ggcttcaaga acagcccgac actcttcaac     4860

gaggcgctcc atagggacct cgcggatttt cgcatccagc atccggacct catcctcctc     4920

cagtatgtgg atgatctcct cctcgccgcg acctccgagc tggattgtca acaaggcaca     4980

cgcgcgctcc tccaaacact cgggaacctc ggctatcgcg cgtccgcgaa aaaggcccaa     5040

atctgccaga agcaagtgaa gtacctcggg tatctgctca aggaaggcca acgctggctc     5100

accgaagcgc gcaaagaaac agtgatgggg caaccgacac cgaaaacacc acgccagctg     5160

cgcgagtttc tcggcaaagc cggcttctgt cgcctcttca tcccgggctt tgccgagatg     5220

gccgcgccac tctacccact caccaagccg ggcacactgt ttaactgggg gccggatcag     5280

cagaaagcct accaagagat caaacaagcg ctcctcaccg ccccagcgct cgggctccca     5340

gatctcacaa agccgttcga gctgttcgtc gatgagaagc aaggctacgc gaagggcgtg     5400

ctcacacaga agctcggccc gtggaggagg ccagtggcct atctctccaa aaaactcgat     5460

ccagtggccg ccggctggcc accgtgtctg cgcatggtcg ccgcgattgc cgtgctcaca     5520

aaggatgccg gcaaactcac aatgggccag ccgctggtga tcctcgcgcc acatgccgtg     5580

gaagccctcg tcaaacagcc gccggatagg tggctctcca atgcgcgcat gacccattac     5640

caagcgctcc tcctcgacac cgatcgcgtc cagttcggcc cagtggtcgc cctcaatccg     5700

gcgacactgc tgccactccc agaggagggc ctccaacaca actgtctgga tattctcgcg     5760

gaagcgcatg gcacaaggcc agacctcaca gatcaaccgc tcccggatgc ggatcacaca     5820

tggtataccg acggctcctc tctgctccaa gagggccaaa ggaaagccgg cgccgcggtg     5880

accacagaaa cagaagtgat ctgggccaag gccctcccag ccggcacatc cgcgcaaagg     5940

gcggaactca tcgcgctcac acaagccctc aagatggccg agggcaagaa gctcaacgtc     6000

tacacagact cccgctatgc cttcgccacc gcccacattc acggcgaaat ctataggagg     6060

cgcggctggc tcacaagcga ggggaaggag atcaagaaca aggatgagat cctcgcgctg     6120

ctcaaggccc tctttctccc gaagcgcctc tccatcatcc actgtccggg ccaccaaaag     6180

gggcactccg cggaagcgag gggcaatagg atggccgatc aagccgcgcg caaagccgcg     6240

attaccgaaa ccccagacac atccaccctc ctcatcgaaa actcctcccc aagcggcggc     6300

agcccgaaga agaaaaggaa ggtgtga                                         6327


<210>  10
<211>  6342
<212>  DNA
<213>  Artificial sequence

<220>
<223>  ںϵnCas9(H840A)-CaMVĻ

<400>  10
atgcctaaga aaaagagaaa agtggacaag aagtactcga tcggcctcga tattgggact       60

aactctgttg gctgggccgt gatcaccgac gagtacaagg tgccctcaaa gaagttcaag      120

gtcctgggca acaccgatcg gcattccatc aagaagaatc tcattggcgc tctcctgttc      180

gacagcggcg agacggctga ggctacgcgg ctcaagcgca ccgcccgcag gcggtacacg      240

cgcaggaaga atcgcatctg ctacctgcag gagattttct ccaacgagat ggcgaaggtt      300

gacgattctt tcttccacag gctggaggag tcattcctcg tggaggagga taagaagcac      360

gagcggcatc caatcttcgg caacattgtc gacgaggttg cctaccacga gaagtaccct      420

acgatctacc atctgcggaa gaagctcgtg gactccacag ataaggcgga cctccgcctg      480

atctacctcg ctctggccca catgattaag ttcaggggcc atttcctgat cgagggggat      540

ctcaacccgg acaatagcga tgttgacaag ctgttcatcc agctcgtgca gacgtacaac      600

cagctcttcg aggagaaccc cattaatgcg tcaggcgtcg acgcgaaggc tatcctgtcc      660

gctaggctct cgaagtctcg gcgcctcgag aacctgatcg cccagctgcc gggcgagaag      720

aagaacggcc tgttcgggaa tctcattgcg ctcagcctgg ggctcacgcc caacttcaag      780

tcgaatttcg atctcgctga ggacgccaag ctgcagctct ccaaggacac atacgacgat      840

gacctggata acctcctggc ccagatcggc gatcagtacg cggacctgtt cctcgctgcc      900

aagaatctgt cggacgccat cctcctgtct gatattctca gggtgaacac cgagattacg      960

aaggctccgc tctcagcctc catgatcaag cgctacgacg agcaccatca ggatctgacc     1020

ctcctgaagg cgctggtcag gcagcagctc cccgagaagt acaaggagat cttcttcgat     1080

cagtcgaaga acggctacgc tgggtacatt gacggcgggg cctctcagga ggagttctac     1140

aagttcatca agccgattct ggagaagatg gacggcacgg aggagctgct ggtgaagctc     1200

aatcgcgagg acctcctgag gaagcagcgg acattcgata acggcagcat cccacaccag     1260

attcatctcg gggagctgca cgctatcctg aggaggcagg aggacttcta ccctttcctc     1320

aaggataacc gcgagaagat cgagaagatt ctgactttca ggatcccgta ctacgtcggc     1380

ccactcgcta ggggcaactc ccgcttcgct tggatgaccc gcaagtcaga ggagacgatc     1440

acgccgtgga acttcgagga ggtggtcgac aagggcgcta gcgctcagtc gttcatcgag     1500

aggatgacga atttcgacaa gaacctgcca aatgagaagg tgctccctaa gcactcgctc     1560

ctgtacgagt acttcacagt ctacaacgag ctgactaagg tgaagtatgt gaccgagggc     1620

atgaggaagc cggctttcct gtctggggag cagaagaagg ccatcgtgga cctcctgttc     1680

aagaccaacc ggaaggtcac ggttaagcag ctcaaggagg actacttcaa gaagattgag     1740

tgcttcgatt cggtcgagat ctctggcgtt gaggaccgct tcaacgcctc cctggggacc     1800

taccacgatc tcctgaagat cattaaggat aaggacttcc tggacaacga ggagaatgag     1860

gatatcctcg aggacattgt gctgacactc actctgttcg aggaccggga gatgatcgag     1920

gagcgcctga agacttacgc ccatctcttc gatgacaagg tcatgaagca gctcaagagg     1980

aggaggtaca ccggctgggg gaggctgagc aggaagctca tcaacggcat tcgggacaag     2040

cagtccggga agacgatcct cgacttcctg aagagcgatg gcttcgcgaa ccgcaatttc     2100

atgcagctga ttcacgatga cagcctcaca ttcaaggagg atatccagaa ggctcaggtg     2160

agcggccagg gggactcgct gcacgagcat atcgcgaacc tcgctggctc gccagctatc     2220

aagaagggga ttctgcagac cgtgaaggtt gtggacgagc tggtgaaggt catgggcagg     2280

cacaagcctg agaacatcgt cattgagatg gcccgggaga atcagaccac gcagaagggc     2340

cagaagaact cacgcgagag gatgaagagg atcgaggagg gcattaagga gctggggtcc     2400

cagatcctca aggagcaccc ggtggagaac acgcagctgc agaatgagaa gctctacctg     2460

tactacctcc agaatggccg cgatatgtat gtggaccagg agctggatat taacaggctc     2520

agcgattacg acgtcgatgc catcgttcca cagtcattcc tgaaggatga ctccattgac     2580

aacaaggtcc tcaccaggtc ggacaagaac cggggcaagt ctgataatgt tccttcagag     2640

gaggtcgtta agaagatgaa gaactactgg cgccagctcc tgaatgccaa gctgatcacg     2700

cagcggaagt tcgataacct cacaaaggct gagaggggcg ggctctctga gctggacaag     2760

gcgggcttca tcaagaggca gctggtcgag acacggcaga tcactaagca cgttgcgcag     2820

attctcgact cacggatgaa cactaagtac gatgagaatg acaagctgat ccgcgaggtg     2880

aaggtcatca ccctgaagtc aaagctcgtc tccgacttca ggaaggattt ccagttctac     2940

aaggttcggg agatcaacaa ttaccaccat gcccatgacg cgtacctgaa cgcggtggtc     3000

ggcacagctc tgatcaagaa gtacccaaag ctcgagagcg agttcgtgta cggggactac     3060

aaggtttacg atgtgaggaa gatgatcgcc aagtcggagc aggagattgg caaggctacc     3120

gccaagtact tcttctactc taacattatg aatttcttca agacagagat cactctggcc     3180

aatggcgaga tccggaagcg ccccctcatc gagacgaacg gcgagacggg ggagatcgtg     3240

tgggacaagg gcagggattt cgcgaccgtc aggaaggttc tctccatgcc acaagtgaat     3300

atcgtcaaga agacagaggt ccagactggc gggttctcta aggagtcaat tctgcctaag     3360

cggaacagcg acaagctcat cgcccgcaag aaggactggg atccgaagaa gtacggcggg     3420

ttcgacagcc ccactgtggc ctactcggtc ctggttgtgg cgaaggttga gaagggcaag     3480

tccaagaagc tcaagagcgt gaaggagctg ctggggatca cgattatgga gcgctccagc     3540

ttcgagaaga acccgatcga tttcctggag gcgaagggct acaaggaggt gaagaaggac     3600

ctgatcatta agctccccaa gtactcactc ttcgagctgg agaacggcag gaagcggatg     3660

ctggcttccg ctggcgagct gcagaagggg aacgagctgg ctctgccgtc caagtatgtg     3720

aacttcctct acctggcctc ccactacgag aagctcaagg gcagccccga ggacaacgag     3780

cagaagcagc tgttcgtcga gcagcacaag cattacctcg acgagatcat tgagcagatt     3840

tccgagttct ccaagcgcgt gatcctggcc gacgcgaatc tggataaggt cctctccgcg     3900

tacaacaagc accgcgacaa gccaatcagg gagcaggctg agaatatcat tcatctcttc     3960

accctgacga acctcggcgc ccctgctgct ttcaagtact tcgacacaac tatcgatcgc     4020

aagaggtaca caagcactaa ggaggtcctg gacgcgaccc tcatccacca gtcgattacc     4080

ggcctctacg agacgcgcat cgacctgtct cagctcgggg gcgacgaatt cccaaagaag     4140

aagcggaagg tggagctcag cggaggatct tccggaggat ctagcggctc cgagacacca     4200

ggaacatccg aaagcgctac accagaatct agcggaggct cttccggagg atctaggcct     4260

gatcatctgc tcctcaagac acagacccag accgagcaag tgatgaatgt gaccaacccg     4320

aactccatct acatcaaggg gcgcctctat ttcaagggct ataagaagat cgaactccat     4380

tgctttgtcg acaccggcgc gtccctctgc atcgcgagca agttcgtcat cccagaagag     4440

cattgggtga acgcggagag gccgatcatg gtgaagatcg ccgacggctc ctccatcacc     4500

atcagcaagg tgtgcaagga tatcgatctc atcatcgccg gcgagatctt ccgcattcca     4560

accgtctacc agcaagagtc cggcatcgac tttattatcg gcaacaactt ctgccagctg     4620

tacgaaccgt tcatccagtt caccgaccgc gtgatcttca caaagaacaa gtcctacccg     4680

gtccacatcg ccaaactgac aagggcggtg agggtgggga cagagggctt tctcgagagc     4740

atgaagaaga ggagcaagac acagcagcca gagccggtga atatcagcac caacaagatc     4800

gaaaacccgc tggaggagat tgccattctc agcgagggga ggaggctctc cgaggagaag     4860

ctctttatta cccagcagcg catgcagaag atcgaagaac tgctcgagaa agtctgctcc     4920

gagaacccac tcgacccgaa taagaccaag cagtggatga aggcgagcat caaactctcc     4980

gatccgagca aagcgatcaa agtgaagccg atgaagtact ccccgatgga tcgcgaggag     5040

ttcgacaagc agattaagga gctgctggac ctcaaagtca tcaagccgtc caaatccccg     5100

cacatggccc cagcctttct cgtgaataat gaggcggaga agaggagggg caagaagagg     5160

atggtcgtga actacaaggc gatgaacaaa gcgaccgtgg gggatgcgta taatctgccg     5220

aacaaggacg agctgctcac actgattcgc ggcaagaaga tcttctccag cttcgattgc     5280

aagtccgggt tctggcaagt gctcctcgac caagaatctc gcccactcac cgcctttaca     5340

tgcccgcaag gccactacga gtggaacgtc gtgccattcg ggctcaagca agccccaagc     5400

atcttccagc gccacatgga tgaagccttc cgcgtgttcc gcaaattctg ctgcgtctac     5460

gtcgatgaca tcctcgtgtt ttccaacaac gaggaggacc acctcctcca tgtggccatg     5520

attctccaga agtgcaatca gcacggcatc attctctcca agaagaaagc gcagctgttc     5580

aagaaaaaaa tcaactttct cggcctcgag attgatgagg gcacccataa gccgcaaggc     5640

catattctcg agcacatcaa caagtttccg gacaccctcg aggacaagaa gcaactgcaa     5700

cgctttctcg gcatcctcac atacgcgagc gactatatcc caaaactcgc ccagatccgc     5760

aagccactcc aagccaaact gaaggaaaac gtcccgtggc gctggaccaa agaggacacc     5820

ctctacatgc agaaagtgaa gaaaaatctc caaggctttc cgccgctgca ccatccactc     5880

ccggaggaaa agctcatcat tgaaaccgac gcgagcgatg attactgggg cgggatgctc     5940

aaggccatca agattaacga gggcaccaac accgaactca tctgtcgcta cgcgtccggg     6000

tcctttaagg cggccgagaa gaactaccac agcaacgata aggaaaccct cgcggtcatc     6060

aacaccatca aaaagttcag catctatctc accccggtgc actttctcat ccgcaccgac     6120

aacacacact ttaagagctt cgtcaacctc aactataagg gcgattccaa gctcgggcgc     6180

aacattaggt ggcaagcgtg gctctcccac tacagctttg acgtcgagca catcaagggc     6240

accgacaacc atttcgccga ctttctcagc cgcgagttca acaaggtcaa ttccagcggg     6300

ggcagcagcg gcggcagccc gaagaagaaa aggaaggtgt ga                        6342


<210>  11
<211>  5280
<212>  DNA
<213>  Artificial sequence

<220>
<223>  ںϵnCas9(H840A)-retronĻ

<400>  11
atgcctaaga aaaagagaaa agtggacaag aagtactcga tcggcctcga tattgggact       60

aactctgttg gctgggccgt gatcaccgac gagtacaagg tgccctcaaa gaagttcaag      120

gtcctgggca acaccgatcg gcattccatc aagaagaatc tcattggcgc tctcctgttc      180

gacagcggcg agacggctga ggctacgcgg ctcaagcgca ccgcccgcag gcggtacacg      240

cgcaggaaga atcgcatctg ctacctgcag gagattttct ccaacgagat ggcgaaggtt      300

gacgattctt tcttccacag gctggaggag tcattcctcg tggaggagga taagaagcac      360

gagcggcatc caatcttcgg caacattgtc gacgaggttg cctaccacga gaagtaccct      420

acgatctacc atctgcggaa gaagctcgtg gactccacag ataaggcgga cctccgcctg      480

atctacctcg ctctggccca catgattaag ttcaggggcc atttcctgat cgagggggat      540

ctcaacccgg acaatagcga tgttgacaag ctgttcatcc agctcgtgca gacgtacaac      600

cagctcttcg aggagaaccc cattaatgcg tcaggcgtcg acgcgaaggc tatcctgtcc      660

gctaggctct cgaagtctcg gcgcctcgag aacctgatcg cccagctgcc gggcgagaag      720

aagaacggcc tgttcgggaa tctcattgcg ctcagcctgg ggctcacgcc caacttcaag      780

tcgaatttcg atctcgctga ggacgccaag ctgcagctct ccaaggacac atacgacgat      840

gacctggata acctcctggc ccagatcggc gatcagtacg cggacctgtt cctcgctgcc      900

aagaatctgt cggacgccat cctcctgtct gatattctca gggtgaacac cgagattacg      960

aaggctccgc tctcagcctc catgatcaag cgctacgacg agcaccatca ggatctgacc     1020

ctcctgaagg cgctggtcag gcagcagctc cccgagaagt acaaggagat cttcttcgat     1080

cagtcgaaga acggctacgc tgggtacatt gacggcgggg cctctcagga ggagttctac     1140

aagttcatca agccgattct ggagaagatg gacggcacgg aggagctgct ggtgaagctc     1200

aatcgcgagg acctcctgag gaagcagcgg acattcgata acggcagcat cccacaccag     1260

attcatctcg gggagctgca cgctatcctg aggaggcagg aggacttcta ccctttcctc     1320

aaggataacc gcgagaagat cgagaagatt ctgactttca ggatcccgta ctacgtcggc     1380

ccactcgcta ggggcaactc ccgcttcgct tggatgaccc gcaagtcaga ggagacgatc     1440

acgccgtgga acttcgagga ggtggtcgac aagggcgcta gcgctcagtc gttcatcgag     1500

aggatgacga atttcgacaa gaacctgcca aatgagaagg tgctccctaa gcactcgctc     1560

ctgtacgagt acttcacagt ctacaacgag ctgactaagg tgaagtatgt gaccgagggc     1620

atgaggaagc cggctttcct gtctggggag cagaagaagg ccatcgtgga cctcctgttc     1680

aagaccaacc ggaaggtcac ggttaagcag ctcaaggagg actacttcaa gaagattgag     1740

tgcttcgatt cggtcgagat ctctggcgtt gaggaccgct tcaacgcctc cctggggacc     1800

taccacgatc tcctgaagat cattaaggat aaggacttcc tggacaacga ggagaatgag     1860

gatatcctcg aggacattgt gctgacactc actctgttcg aggaccggga gatgatcgag     1920

gagcgcctga agacttacgc ccatctcttc gatgacaagg tcatgaagca gctcaagagg     1980

aggaggtaca ccggctgggg gaggctgagc aggaagctca tcaacggcat tcgggacaag     2040

cagtccggga agacgatcct cgacttcctg aagagcgatg gcttcgcgaa ccgcaatttc     2100

atgcagctga ttcacgatga cagcctcaca ttcaaggagg atatccagaa ggctcaggtg     2160

agcggccagg gggactcgct gcacgagcat atcgcgaacc tcgctggctc gccagctatc     2220

aagaagggga ttctgcagac cgtgaaggtt gtggacgagc tggtgaaggt catgggcagg     2280

cacaagcctg agaacatcgt cattgagatg gcccgggaga atcagaccac gcagaagggc     2340

cagaagaact cacgcgagag gatgaagagg atcgaggagg gcattaagga gctggggtcc     2400

cagatcctca aggagcaccc ggtggagaac acgcagctgc agaatgagaa gctctacctg     2460

tactacctcc agaatggccg cgatatgtat gtggaccagg agctggatat taacaggctc     2520

agcgattacg acgtcgatgc catcgttcca cagtcattcc tgaaggatga ctccattgac     2580

aacaaggtcc tcaccaggtc ggacaagaac cggggcaagt ctgataatgt tccttcagag     2640

gaggtcgtta agaagatgaa gaactactgg cgccagctcc tgaatgccaa gctgatcacg     2700

cagcggaagt tcgataacct cacaaaggct gagaggggcg ggctctctga gctggacaag     2760

gcgggcttca tcaagaggca gctggtcgag acacggcaga tcactaagca cgttgcgcag     2820

attctcgact cacggatgaa cactaagtac gatgagaatg acaagctgat ccgcgaggtg     2880

aaggtcatca ccctgaagtc aaagctcgtc tccgacttca ggaaggattt ccagttctac     2940

aaggttcggg agatcaacaa ttaccaccat gcccatgacg cgtacctgaa cgcggtggtc     3000

ggcacagctc tgatcaagaa gtacccaaag ctcgagagcg agttcgtgta cggggactac     3060

aaggtttacg atgtgaggaa gatgatcgcc aagtcggagc aggagattgg caaggctacc     3120

gccaagtact tcttctactc taacattatg aatttcttca agacagagat cactctggcc     3180

aatggcgaga tccggaagcg ccccctcatc gagacgaacg gcgagacggg ggagatcgtg     3240

tgggacaagg gcagggattt cgcgaccgtc aggaaggttc tctccatgcc acaagtgaat     3300

atcgtcaaga agacagaggt ccagactggc gggttctcta aggagtcaat tctgcctaag     3360

cggaacagcg acaagctcat cgcccgcaag aaggactggg atccgaagaa gtacggcggg     3420

ttcgacagcc ccactgtggc ctactcggtc ctggttgtgg cgaaggttga gaagggcaag     3480

tccaagaagc tcaagagcgt gaaggagctg ctggggatca cgattatgga gcgctccagc     3540

ttcgagaaga acccgatcga tttcctggag gcgaagggct acaaggaggt gaagaaggac     3600

ctgatcatta agctccccaa gtactcactc ttcgagctgg agaacggcag gaagcggatg     3660

ctggcttccg ctggcgagct gcagaagggg aacgagctgg ctctgccgtc caagtatgtg     3720

aacttcctct acctggcctc ccactacgag aagctcaagg gcagccccga ggacaacgag     3780

cagaagcagc tgttcgtcga gcagcacaag cattacctcg acgagatcat tgagcagatt     3840

tccgagttct ccaagcgcgt gatcctggcc gacgcgaatc tggataaggt cctctccgcg     3900

tacaacaagc accgcgacaa gccaatcagg gagcaggctg agaatatcat tcatctcttc     3960

accctgacga acctcggcgc ccctgctgct ttcaagtact tcgacacaac tatcgatcgc     4020

aagaggtaca caagcactaa ggaggtcctg gacgcgaccc tcatccacca gtcgattacc     4080

ggcctctacg agacgcgcat cgacctgtct cagctcgggg gcgacgaatt cccaaagaag     4140

aagcggaagg tggagctcag cggaggatct tccggaggat ctagcggctc cgagacacca     4200

ggaacatccg aaagcgctac accagaatct agcggaggct cttccggagg atctaggcct     4260

ggtattcacg gcgttcctgc ggcgatgaag tcggctgagt acctgaacac cttccggctg     4320

agaaacctcg ggctgccagt gatgaacaac ctccacgata tgtctaaggc tacccggatc     4380

tccgttgaga cgctgagact cctgatctac accgctgact tccggtacag aatctacacg     4440

gtggagaaga aggggcccga gaagaggatg cgcaccatct accaacctag cagagagctc     4500

aaggcgctgc agggctgggt gctgagaaac atcctcgata agctgtccag ctcgcccttc     4560

tctatcgggt tcgagaagca ccaatccatc ctcaacaacg ccacccctca tatcggcgcg     4620

aacttcatcc tcaacatcga cctggaggat ttcttcccca gcctcacggc caacaaggtt     4680

ttcggggtgt tccactcgct cggctacaac aggctgatct catctgtcct caccaagatc     4740

tgctgctaca agaacctcct gcctcaaggc gctccatcca gcccgaagct cgccaacctg     4800

atctgctcaa agctggacta ccgcatccag ggctacgctg ggtccagggg cctcatctac     4860

acccgctacg cggacgatct cacgctgagc gctcagtcga tgaagaaggt ggtcaaggcg     4920

cgggatttcc tgttctcaat catcccatct gagggcctcg tcatcaacag caagaagacc     4980

tgcatctccg ggccgcggag ccaaagaaag gtcacgggcc tggttatctc ccaggagaag     5040

gttggcatcg ggagggagaa gtacaaggag atccgcgcca agatccacca tatcttctgc     5100

gggaagtcgt cagagatcga gcacgtgcgc ggctggctct cgttcatcct gtcagtcgac     5160

tctaagtccc ataggcgcct catcacctac atctctaagc tggagaagaa gtacggcaag     5220

aaccccctga acaaggctaa gaccagcggc ggcagcccga agaagaaaag gaaggtgtga     5280


<210>  12
<211>  2108
<212>  PRT
<213>  Artificial sequence

<220>
<223>  ںϵnCas9(H840A)-M-MLVİ

<400>  12

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Leu Ser  Gln Leu Gly Gly Asp  Glu Phe Pro Lys Lys  Lys Arg Lys 
    1370                 1375                 1380             


Val Glu  Leu Ser Gly Gly Ser  Ser Gly Gly Ser Ser  Gly Ser Glu 
    1385                 1390                 1395             


Thr Pro  Gly Thr Ser Glu Ser  Ala Thr Pro Glu Ser  Ser Gly Gly 
    1400                 1405                 1410             


Ser Ser  Gly Gly Ser Arg Pro  Thr Leu Asn Ile Glu  Asp Glu Tyr 
    1415                 1420                 1425             


Arg Leu  His Glu Thr Ser Lys  Glu Pro Asp Val Ser  Leu Gly Ser 
    1430                 1435                 1440             


Thr Trp  Leu Ser Asp Phe Pro  Gln Ala Trp Ala Glu  Thr Gly Gly 
    1445                 1450                 1455             


Met Gly  Leu Ala Val Arg Gln  Ala Pro Leu Ile Ile  Pro Leu Lys 
    1460                 1465                 1470             


Ala Thr  Ser Thr Pro Val Ser  Ile Lys Gln Tyr Pro  Met Ser Gln 
    1475                 1480                 1485             


Glu Ala  Arg Leu Gly Ile Lys  Pro His Ile Gln Arg  Leu Leu Asp 
    1490                 1495                 1500             


Gln Gly  Ile Leu Val Pro Cys  Gln Ser Pro Trp Asn  Thr Pro Leu 
    1505                 1510                 1515             


Leu Pro  Val Lys Lys Pro Gly  Thr Asn Asp Tyr Arg  Pro Val Gln 
    1520                 1525                 1530             


Asp Leu  Arg Glu Val Asn Lys  Arg Val Glu Asp Ile  His Pro Thr 
    1535                 1540                 1545             


Val Pro  Asn Pro Tyr Asn Leu  Leu Ser Gly Leu Pro  Pro Ser His 
    1550                 1555                 1560             


Gln Trp  Tyr Thr Val Leu Asp  Leu Lys Asp Ala Phe  Phe Cys Leu 
    1565                 1570                 1575             


Arg Leu  His Pro Thr Ser Gln  Pro Leu Phe Ala Phe  Glu Trp Arg 
    1580                 1585                 1590             


Asp Pro  Glu Met Gly Ile Ser  Gly Gln Leu Thr Trp  Thr Arg Leu 
    1595                 1600                 1605             


Pro Gln  Gly Phe Lys Asn Ser  Pro Thr Leu Phe Asn  Glu Ala Leu 
    1610                 1615                 1620             


His Arg  Asp Leu Ala Asp Phe  Arg Ile Gln His Pro  Asp Leu Ile 
    1625                 1630                 1635             


Leu Leu  Gln Tyr Val Asp Asp  Leu Leu Leu Ala Ala  Thr Ser Glu 
    1640                 1645                 1650             


Leu Asp  Cys Gln Gln Gly Thr  Arg Ala Leu Leu Gln  Thr Leu Gly 
    1655                 1660                 1665             


Asn Leu  Gly Tyr Arg Ala Ser  Ala Lys Lys Ala Gln  Ile Cys Gln 
    1670                 1675                 1680             


Lys Gln  Val Lys Tyr Leu Gly  Tyr Leu Leu Lys Glu  Gly Gln Arg 
    1685                 1690                 1695             


Trp Leu  Thr Glu Ala Arg Lys  Glu Thr Val Met Gly  Gln Pro Thr 
    1700                 1705                 1710             


Pro Lys  Thr Pro Arg Gln Leu  Arg Glu Phe Leu Gly  Lys Ala Gly 
    1715                 1720                 1725             


Phe Cys  Arg Leu Phe Ile Pro  Gly Phe Ala Glu Met  Ala Ala Pro 
    1730                 1735                 1740             


Leu Tyr  Pro Leu Thr Lys Pro  Gly Thr Leu Phe Asn  Trp Gly Pro 
    1745                 1750                 1755             


Asp Gln  Gln Lys Ala Tyr Gln  Glu Ile Lys Gln Ala  Leu Leu Thr 
    1760                 1765                 1770             


Ala Pro  Ala Leu Gly Leu Pro  Asp Leu Thr Lys Pro  Phe Glu Leu 
    1775                 1780                 1785             


Phe Val  Asp Glu Lys Gln Gly  Tyr Ala Lys Gly Val  Leu Thr Gln 
    1790                 1795                 1800             


Lys Leu  Gly Pro Trp Arg Arg  Pro Val Ala Tyr Leu  Ser Lys Lys 
    1805                 1810                 1815             


Leu Asp  Pro Val Ala Ala Gly  Trp Pro Pro Cys Leu  Arg Met Val 
    1820                 1825                 1830             


Ala Ala  Ile Ala Val Leu Thr  Lys Asp Ala Gly Lys  Leu Thr Met 
    1835                 1840                 1845             


Gly Gln  Pro Leu Val Ile Leu  Ala Pro His Ala Val  Glu Ala Leu 
    1850                 1855                 1860             


Val Lys  Gln Pro Pro Asp Arg  Trp Leu Ser Asn Ala  Arg Met Thr 
    1865                 1870                 1875             


His Tyr  Gln Ala Leu Leu Leu  Asp Thr Asp Arg Val  Gln Phe Gly 
    1880                 1885                 1890             


Pro Val  Val Ala Leu Asn Pro  Ala Thr Leu Leu Pro  Leu Pro Glu 
    1895                 1900                 1905             


Glu Gly  Leu Gln His Asn Cys  Leu Asp Ile Leu Ala  Glu Ala His 
    1910                 1915                 1920             


Gly Thr  Arg Pro Asp Leu Thr  Asp Gln Pro Leu Pro  Asp Ala Asp 
    1925                 1930                 1935             


His Thr  Trp Tyr Thr Asp Gly  Ser Ser Leu Leu Gln  Glu Gly Gln 
    1940                 1945                 1950             


Arg Lys  Ala Gly Ala Ala Val  Thr Thr Glu Thr Glu  Val Ile Trp 
    1955                 1960                 1965             


Ala Lys  Ala Leu Pro Ala Gly  Thr Ser Ala Gln Arg  Ala Glu Leu 
    1970                 1975                 1980             


Ile Ala  Leu Thr Gln Ala Leu  Lys Met Ala Glu Gly  Lys Lys Leu 
    1985                 1990                 1995             


Asn Val  Tyr Thr Asp Ser Arg  Tyr Ala Phe Ala Thr  Ala His Ile 
    2000                 2005                 2010             


His Gly  Glu Ile Tyr Arg Arg  Arg Gly Trp Leu Thr  Ser Glu Gly 
    2015                 2020                 2025             


Lys Glu  Ile Lys Asn Lys Asp  Glu Ile Leu Ala Leu  Leu Lys Ala 
    2030                 2035                 2040             


Leu Phe  Leu Pro Lys Arg Leu  Ser Ile Ile His Cys  Pro Gly His 
    2045                 2050                 2055             


Gln Lys  Gly His Ser Ala Glu  Ala Arg Gly Asn Arg  Met Ala Asp 
    2060                 2065                 2070             


Gln Ala  Ala Arg Lys Ala Ala  Ile Thr Glu Thr Pro  Asp Thr Ser 
    2075                 2080                 2085             


Thr Leu  Leu Ile Glu Asn Ser  Ser Pro Ser Gly Gly  Ser Pro Lys 
    2090                 2095                 2100             


Lys Lys  Arg Lys Val 
    2105             


<210>  13
<211>  2113
<212>  PRT
<213>  Artificial sequence

<220>
<223>  ںϵnCas9(H840A)-CaMVİ

<400>  13

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Leu Ser  Gln Leu Gly Gly Asp  Glu Phe Pro Lys Lys  Lys Arg Lys 
    1370                 1375                 1380             


Val Glu  Leu Ser Gly Gly Ser  Ser Gly Gly Ser Ser  Gly Ser Glu 
    1385                 1390                 1395             


Thr Pro  Gly Thr Ser Glu Ser  Ala Thr Pro Glu Ser  Ser Gly Gly 
    1400                 1405                 1410             


Ser Ser  Gly Gly Ser Arg Pro  Asp His Leu Leu Leu  Lys Thr Gln 
    1415                 1420                 1425             


Thr Gln  Thr Glu Gln Val Met  Asn Val Thr Asn Pro  Asn Ser Ile 
    1430                 1435                 1440             


Tyr Ile  Lys Gly Arg Leu Tyr  Phe Lys Gly Tyr Lys  Lys Ile Glu 
    1445                 1450                 1455             


Leu His  Cys Phe Val Asp Thr  Gly Ala Ser Leu Cys  Ile Ala Ser 
    1460                 1465                 1470             


Lys Phe  Val Ile Pro Glu Glu  His Trp Val Asn Ala  Glu Arg Pro 
    1475                 1480                 1485             


Ile Met  Val Lys Ile Ala Asp  Gly Ser Ser Ile Thr  Ile Ser Lys 
    1490                 1495                 1500             


Val Cys  Lys Asp Ile Asp Leu  Ile Ile Ala Gly Glu  Ile Phe Arg 
    1505                 1510                 1515             


Ile Pro  Thr Val Tyr Gln Gln  Glu Ser Gly Ile Asp  Phe Ile Ile 
    1520                 1525                 1530             


Gly Asn  Asn Phe Cys Gln Leu  Tyr Glu Pro Phe Ile  Gln Phe Thr 
    1535                 1540                 1545             


Asp Arg  Val Ile Phe Thr Lys  Asn Lys Ser Tyr Pro  Val His Ile 
    1550                 1555                 1560             


Ala Lys  Leu Thr Arg Ala Val  Arg Val Gly Thr Glu  Gly Phe Leu 
    1565                 1570                 1575             


Glu Ser  Met Lys Lys Arg Ser  Lys Thr Gln Gln Pro  Glu Pro Val 
    1580                 1585                 1590             


Asn Ile  Ser Thr Asn Lys Ile  Glu Asn Pro Leu Glu  Glu Ile Ala 
    1595                 1600                 1605             


Ile Leu  Ser Glu Gly Arg Arg  Leu Ser Glu Glu Lys  Leu Phe Ile 
    1610                 1615                 1620             


Thr Gln  Gln Arg Met Gln Lys  Ile Glu Glu Leu Leu  Glu Lys Val 
    1625                 1630                 1635             


Cys Ser  Glu Asn Pro Leu Asp  Pro Asn Lys Thr Lys  Gln Trp Met 
    1640                 1645                 1650             


Lys Ala  Ser Ile Lys Leu Ser  Asp Pro Ser Lys Ala  Ile Lys Val 
    1655                 1660                 1665             


Lys Pro  Met Lys Tyr Ser Pro  Met Asp Arg Glu Glu  Phe Asp Lys 
    1670                 1675                 1680             


Gln Ile  Lys Glu Leu Leu Asp  Leu Lys Val Ile Lys  Pro Ser Lys 
    1685                 1690                 1695             


Ser Pro  His Met Ala Pro Ala  Phe Leu Val Asn Asn  Glu Ala Glu 
    1700                 1705                 1710             


Lys Arg  Arg Gly Lys Lys Arg  Met Val Val Asn Tyr  Lys Ala Met 
    1715                 1720                 1725             


Asn Lys  Ala Thr Val Gly Asp  Ala Tyr Asn Leu Pro  Asn Lys Asp 
    1730                 1735                 1740             


Glu Leu  Leu Thr Leu Ile Arg  Gly Lys Lys Ile Phe  Ser Ser Phe 
    1745                 1750                 1755             


Asp Cys  Lys Ser Gly Phe Trp  Gln Val Leu Leu Asp  Gln Glu Ser 
    1760                 1765                 1770             


Arg Pro  Leu Thr Ala Phe Thr  Cys Pro Gln Gly His  Tyr Glu Trp 
    1775                 1780                 1785             


Asn Val  Val Pro Phe Gly Leu  Lys Gln Ala Pro Ser  Ile Phe Gln 
    1790                 1795                 1800             


Arg His  Met Asp Glu Ala Phe  Arg Val Phe Arg Lys  Phe Cys Cys 
    1805                 1810                 1815             


Val Tyr  Val Asp Asp Ile Leu  Val Phe Ser Asn Asn  Glu Glu Asp 
    1820                 1825                 1830             


His Leu  Leu His Val Ala Met  Ile Leu Gln Lys Cys  Asn Gln His 
    1835                 1840                 1845             


Gly Ile  Ile Leu Ser Lys Lys  Lys Ala Gln Leu Phe  Lys Lys Lys 
    1850                 1855                 1860             


Ile Asn  Phe Leu Gly Leu Glu  Ile Asp Glu Gly Thr  His Lys Pro 
    1865                 1870                 1875             


Gln Gly  His Ile Leu Glu His  Ile Asn Lys Phe Pro  Asp Thr Leu 
    1880                 1885                 1890             


Glu Asp  Lys Lys Gln Leu Gln  Arg Phe Leu Gly Ile  Leu Thr Tyr 
    1895                 1900                 1905             


Ala Ser  Asp Tyr Ile Pro Lys  Leu Ala Gln Ile Arg  Lys Pro Leu 
    1910                 1915                 1920             


Gln Ala  Lys Leu Lys Glu Asn  Val Pro Trp Arg Trp  Thr Lys Glu 
    1925                 1930                 1935             


Asp Thr  Leu Tyr Met Gln Lys  Val Lys Lys Asn Leu  Gln Gly Phe 
    1940                 1945                 1950             


Pro Pro  Leu His His Pro Leu  Pro Glu Glu Lys Leu  Ile Ile Glu 
    1955                 1960                 1965             


Thr Asp  Ala Ser Asp Asp Tyr  Trp Gly Gly Met Leu  Lys Ala Ile 
    1970                 1975                 1980             


Lys Ile  Asn Glu Gly Thr Asn  Thr Glu Leu Ile Cys  Arg Tyr Ala 
    1985                 1990                 1995             


Ser Gly  Ser Phe Lys Ala Ala  Glu Lys Asn Tyr His  Ser Asn Asp 
    2000                 2005                 2010             


Lys Glu  Thr Leu Ala Val Ile  Asn Thr Ile Lys Lys  Phe Ser Ile 
    2015                 2020                 2025             


Tyr Leu  Thr Pro Val His Phe  Leu Ile Arg Thr Asp  Asn Thr His 
    2030                 2035                 2040             


Phe Lys  Ser Phe Val Asn Leu  Asn Tyr Lys Gly Asp  Ser Lys Leu 
    2045                 2050                 2055             


Gly Arg  Asn Ile Arg Trp Gln  Ala Trp Leu Ser His  Tyr Ser Phe 
    2060                 2065                 2070             


Asp Val  Glu His Ile Lys Gly  Thr Asp Asn His Phe  Ala Asp Phe 
    2075                 2080                 2085             


Leu Ser  Arg Glu Phe Asn Lys  Val Asn Ser Ser Gly  Gly Ser Ser 
    2090                 2095                 2100             


Gly Gly  Ser Pro Lys Lys Lys  Arg Lys Val 
    2105                 2110             


<210>  14
<211>  1759
<212>  PRT
<213>  Artificial sequence

<220>
<223>  ںϵnCas9(H840A)-retronİ

<400>  14

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Leu Ser  Gln Leu Gly Gly Asp  Glu Phe Pro Lys Lys  Lys Arg Lys 
    1370                 1375                 1380             


Val Glu  Leu Ser Gly Gly Ser  Ser Gly Gly Ser Ser  Gly Ser Glu 
    1385                 1390                 1395             


Thr Pro  Gly Thr Ser Glu Ser  Ala Thr Pro Glu Ser  Ser Gly Gly 
    1400                 1405                 1410             


Ser Ser  Gly Gly Ser Arg Pro  Gly Ile His Gly Val  Pro Ala Ala 
    1415                 1420                 1425             


Met Lys  Ser Ala Glu Tyr Leu  Asn Thr Phe Arg Leu  Arg Asn Leu 
    1430                 1435                 1440             


Gly Leu  Pro Val Met Asn Asn  Leu His Asp Met Ser  Lys Ala Thr 
    1445                 1450                 1455             


Arg Ile  Ser Val Glu Thr Leu  Arg Leu Leu Ile Tyr  Thr Ala Asp 
    1460                 1465                 1470             


Phe Arg  Tyr Arg Ile Tyr Thr  Val Glu Lys Lys Gly  Pro Glu Lys 
    1475                 1480                 1485             


Arg Met  Arg Thr Ile Tyr Gln  Pro Ser Arg Glu Leu  Lys Ala Leu 
    1490                 1495                 1500             


Gln Gly  Trp Val Leu Arg Asn  Ile Leu Asp Lys Leu  Ser Ser Ser 
    1505                 1510                 1515             


Pro Phe  Ser Ile Gly Phe Glu  Lys His Gln Ser Ile  Leu Asn Asn 
    1520                 1525                 1530             


Ala Thr  Pro His Ile Gly Ala  Asn Phe Ile Leu Asn  Ile Asp Leu 
    1535                 1540                 1545             


Glu Asp  Phe Phe Pro Ser Leu  Thr Ala Asn Lys Val  Phe Gly Val 
    1550                 1555                 1560             


Phe His  Ser Leu Gly Tyr Asn  Arg Leu Ile Ser Ser  Val Leu Thr 
    1565                 1570                 1575             


Lys Ile  Cys Cys Tyr Lys Asn  Leu Leu Pro Gln Gly  Ala Pro Ser 
    1580                 1585                 1590             


Ser Pro  Lys Leu Ala Asn Leu  Ile Cys Ser Lys Leu  Asp Tyr Arg 
    1595                 1600                 1605             


Ile Gln  Gly Tyr Ala Gly Ser  Arg Gly Leu Ile Tyr  Thr Arg Tyr 
    1610                 1615                 1620             


Ala Asp  Asp Leu Thr Leu Ser  Ala Gln Ser Met Lys  Lys Val Val 
    1625                 1630                 1635             


Lys Ala  Arg Asp Phe Leu Phe  Ser Ile Ile Pro Ser  Glu Gly Leu 
    1640                 1645                 1650             


Val Ile  Asn Ser Lys Lys Thr  Cys Ile Ser Gly Pro  Arg Ser Gln 
    1655                 1660                 1665             


Arg Lys  Val Thr Gly Leu Val  Ile Ser Gln Glu Lys  Val Gly Ile 
    1670                 1675                 1680             


Gly Arg  Glu Lys Tyr Lys Glu  Ile Arg Ala Lys Ile  His His Ile 
    1685                 1690                 1695             


Phe Cys  Gly Lys Ser Ser Glu  Ile Glu His Val Arg  Gly Trp Leu 
    1700                 1705                 1710             


Ser Phe  Ile Leu Ser Val Asp  Ser Lys Ser His Arg  Arg Leu Ile 
    1715                 1720                 1725             


Thr Tyr  Ile Ser Lys Leu Glu  Lys Lys Tyr Gly Lys  Asn Pro Leu 
    1730                 1735                 1740             


Asn Lys  Ala Lys Thr Ser Gly  Gly Ser Pro Lys Lys  Lys Arg Lys 
    1745                 1750                 1755             


Val 
    


