                         SEQUENCE LISTING

<110>  Mammoth Biosciences, Inc.
 
<120>  EFFECTOR PROTEINS AND METHODS OF USE

<130>  MABI-017/01WO 344183-2144

<150>  US 63/229,951
<151>  2021-08-05

<150>  US 63/187,298
<151>  2021-05-11

<160>  57    

<170>  PatentIn version 3.5

<210>  1
<211>  1226
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CasM.21544

<400>  1

Met Lys Asn Phe Phe Gln Leu Phe Thr Asn Gln Tyr Glu Leu Ser Lys 
1               5                   10                  15      


Thr Leu Arg Phe Glu Leu Arg Pro Ile Glu Asn Thr Ala Glu Leu Leu 
            20                  25                  30          


Lys Lys Asn Lys Ile Phe Glu Lys Asp Lys Lys Val Tyr Glu Tyr Tyr 
        35                  40                  45              


Gln Lys Thr Lys Lys Tyr Phe Asp Lys Leu His Cys Glu Phe Ile Asp 
    50                  55                  60                  


Glu Ala Leu Val Asn Thr Ser Leu Pro Asn Lys Asp Tyr Ser Ile Tyr 
65                  70                  75                  80  


Asp Lys Leu Phe Phe Glu Tyr Lys Lys Asp Lys Glu Asn Lys Lys Ile 
                85                  90                  95      


Tyr Lys Ala Leu Asn Glu His Ala Lys Lys Leu Arg Thr Asn Ile Val 
            100                 105                 110         


Lys Asp Phe Glu Lys Thr Ala Glu Lys Trp Arg Asp Glu Tyr Ile Leu 
        115                 120                 125             


Ser Ile Lys Asp Glu Lys Ser Gln Lys Lys Leu Lys Gln Leu Glu Gly 
    130                 135                 140                 


Leu Asp Leu Leu Phe Lys Thr Glu Val Phe Asp Phe Leu Lys Lys Lys 
145                 150                 155                 160 


Tyr Pro Glu Ala Gln Ile Glu Gly Asn Ser Ile Phe Asp Ser Phe Asn 
                165                 170                 175     


Lys Phe Phe Thr Tyr Phe Asp Asn Phe His Gln Ser Arg Lys Asn Phe 
            180                 185                 190         


Tyr Lys Asp Asp Gly Thr Ala Ser Ala Ile Pro Thr Arg Ile Ile Asp 
        195                 200                 205             


Asp Asn Leu Pro Lys Phe Leu Glu Asn Lys Lys Ile Phe Glu Glu Glu 
    210                 215                 220                 


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


Asp Phe Tyr Asn Lys Cys Phe Thr Gln Thr Gly Ile Glu Asn Tyr Asn 
                245                 250                 255     


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


Asn Lys Lys Ser Lys Ile His Phe Met Lys Glu Leu Phe Lys Gln Ile 
        275                 280                 285             


Leu Ser Lys Arg Ser Lys Gln Ala Thr Glu Gln Asp Thr Ser Ile Ser 
    290                 295                 300                 


Ile Glu Asn Asp Ser Gln Val Phe Glu Val Leu Gln Asp Phe Ile Met 
305                 310                 315                 320 


Glu Thr Lys Asn Cys Asn Arg Met Ala Lys Asn Ile Leu Glu Thr Phe 
                325                 330                 335     


Ile Gln His Gln Glu Glu Phe Asp Leu Gln Lys Val Phe Leu Lys Gly 
            340                 345                 350         


Ser Asn Val Thr Arg Ile Ser Asp Met Trp Phe Thr Ser Trp Phe Ala 
        355                 360                 365             


Phe Gly Asp Leu Leu Pro Lys Asn Ser Thr Gly Lys Lys Leu Ala Asn 
    370                 375                 380                 


Phe Ile Ser Phe Gln Asp Ile Lys Asn Ala Leu Glu Lys Thr Glu Ile 
385                 390                 395                 400 


Gln Asp Val Phe Lys Lys Lys Tyr Ala Lys Tyr Asn Lys Glu Ser Phe 
                405                 410                 415     


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


Asn Asp Cys Glu Lys Asn Ile Val Glu Ala Glu Lys Met Met Lys Val 
        435                 440                 445             


Asp Lys Val Tyr Ser Asn Lys Lys Gly Ile Leu Arg Asn Gly Lys Asn 
    450                 455                 460                 


Gly Glu Lys Gln Lys Glu Ile Ile Lys Asp Phe Ala Asp Ser Ala Leu 
465                 470                 475                 480 


Ser Ile Tyr Gln Met Met Lys Tyr Phe Ala Leu Glu Lys Gly Lys Lys 
                485                 490                 495     


Pro Val Thr Asp Met Asp Glu Asp Pro Arg Phe Tyr Asn Asp Tyr Lys 
            500                 505                 510         


Asp Trp Cys Glu Lys Ser Arg Thr Leu Leu Tyr Tyr Asn Glu Phe Arg 
        515                 520                 525             


Asn Tyr Leu Thr Lys Lys Pro Tyr Ala Glu Asp Lys Ile Lys Leu Asn 
    530                 535                 540                 


Phe Glu Lys Ser Thr Leu Leu Met Gly Trp Ser Ala Asn Glu Glu Gly 
545                 550                 555                 560 


Asn Leu Gln Tyr Tyr Ser Ser Ile Leu Arg Lys Asp Asn Lys Tyr Tyr 
                565                 570                 575     


Leu Gly Leu Met Ser Ser Ala Ser Thr Phe Asn Ile Asn Lys Lys Glu 
            580                 585                 590         


Ala Phe Glu Thr Arg Asp Gly Phe Tyr Glu Leu Met Asn Tyr Arg Gln 
        595                 600                 605             


Leu Lys Ser Thr Thr Ile Tyr Gly Ser Leu Tyr Lys Gly Glu Tyr Lys 
    610                 615                 620                 


Lys Glu Tyr Arg Lys Asp Lys Glu Thr Leu Thr Asn Gln Glu Leu Ile 
625                 630                 635                 640 


Glu Arg Thr Lys Lys Ile Leu Glu Lys Gln Lys Phe Ser Tyr Pro Gln 
                645                 650                 655     


Leu Glu Val Ile Leu Asp Lys Lys Tyr Lys Ala Ala Glu Asp Leu Ala 
            660                 665                 670         


Lys Asp Leu Gly Asn Ile Val Leu Tyr Asn Ile Gly Phe Val Lys Ile 
        675                 680                 685             


Ser Lys Arg Tyr Val Asn Asn Leu Thr Asn Glu Asn Phe Tyr Leu Phe 
    690                 695                 700                 


Glu Ile Ser Asn Lys Asp Phe Leu Asn Lys Lys Lys Lys Gly Asn Val 
705                 710                 715                 720 


Asn Leu His Thr Lys Tyr Phe Gln Leu Leu Phe Asp Lys Lys Asn Leu 
                725                 730                 735     


Glu Ser Lys Lys Gly Ala Ile Leu Lys Leu Ser Gly Gly Gly Glu Val 
            740                 745                 750         


Phe Tyr Arg Lys Ala Thr Lys Asn Leu Pro Lys Lys Lys Asp Lys Lys 
        755                 760                 765             


Gly Lys Glu Ile Ile Asp Arg Lys Arg Tyr Ala Glu Asp Lys Ile Leu 
    770                 775                 780                 


Phe His Leu Pro Ile Val Leu Asn Ile Gly Phe Lys Asp Lys Gln Ile 
785                 790                 795                 800 


Asn Ser Lys Val Asn Gln Val Leu Ala Thr Gln Arg Lys Ala Arg Ile 
                805                 810                 815     


Ile Gly Ile Asp Arg Gly Glu Lys His Leu Leu Tyr Ile Ser Val Ile 
            820                 825                 830         


Asp Glu Asn Ala Asn Ile Leu Lys Ile Lys Ser Leu Asn Thr Ile Asp 
        835                 840                 845             


Val Pro Asn Lys Lys Glu Pro Asp Asp Tyr His Lys Leu Leu Asp Glu 
    850                 855                 860                 


Lys Glu Lys Glu Arg Asp Asp Glu Arg Lys Ser Trp His Thr Ile Glu 
865                 870                 875                 880 


Asn Ile Lys Glu Leu Lys His Gly Tyr Ile Ser Gln Val Val Asn Glu 
                885                 890                 895     


Ile Asp Lys Ile Ile Phe Glu Cys Leu Asp Glu Arg Ile Leu Pro Ile 
            900                 905                 910         


Ile Val Phe Glu Asp Leu Asn Ile Gly Phe Lys Arg Gly Arg Phe Lys 
        915                 920                 925             


Ile Glu Lys Gln Val Tyr Gln Lys Phe Glu Leu Ala Leu Ala Lys Lys 
    930                 935                 940                 


Leu Asn Tyr Leu Val Ser Lys Glu Lys Gly Asn Tyr Leu Asn Ala Phe 
945                 950                 955                 960 


Gln Phe Thr Pro Pro Val Asn Asn Phe Gln Asp Ile His Lys Lys Gln 
                965                 970                 975     


Val Gly Ile Ile Phe Tyr Ile Pro Ala Ser Phe Thr Ser Ala Ile Cys 
            980                 985                 990         


Pro Val Cys Gly Phe Arg Lys Arg  Leu Tyr Gly Phe Thr  Phe Lys Asn 
        995                 1000                 1005             


Ile Asn  Gln Val Lys Lys Leu  Leu Ala Glu His Glu  Phe Asn Ile 
    1010                 1015                 1020             


Phe Tyr  Asp Gly Lys Arg Phe  Asn Phe Glu Cys Leu  Ala Ser Lys 
    1025                 1030                 1035             


Glu Asn  Glu Lys Lys Glu Asn  Lys Asn Gly Leu Tyr  Thr Glu Ile 
    1040                 1045                 1050             


Phe Leu  Asn Lys Lys Leu Phe  Phe Asn Ser Asp Ile  Glu Arg Leu 
    1055                 1060                 1065             


Phe Asn  Lys Lys Ser Lys Asp  Asn Lys Lys Trp Glu  Thr Ile Ser 
    1070                 1075                 1080             


Phe Ile  Ala Thr Glu Glu Leu  Lys Lys Leu Phe Glu  Gly Lys Ile 
    1085                 1090                 1095             


Asp Leu  Lys Arg Asn Ile Met  Asp Gln Ile Leu Ala  Gly Asp Phe 
    1100                 1105                 1110             


Arg Ala  Glu Phe Tyr Gln Gln  Leu Ile Phe Ile Ile  Asn Arg Ile 
    1115                 1120                 1125             


Leu Asn  Leu Arg Asn Cys His  Ala Val Glu His Arg  Asp Phe Ile 
    1130                 1135                 1140             


Ala Cys  Pro Ser Cys Gly Phe  His Ser Glu Lys Asn  Tyr Glu Lys 
    1145                 1150                 1155             


Leu Lys  Ser Arg Tyr Ala Gly  Lys Glu Lys Phe Glu  Phe Asn Gly 
    1160                 1165                 1170             


Asp Ala  Asn Gly Ala Tyr Asn  Ile Ala Arg Lys Gly  Ile Leu Leu 
    1175                 1180                 1185             


Ile Lys  Lys Ile Arg Gln Phe  Ala Lys Ser Asn Asn  Ile Glu Lys 
    1190                 1195                 1200             


Leu Met  Pro Tyr Asp His Leu  Gln Ile Asp Met Gln  Glu Trp Asp 
    1205                 1210                 1215             


Lys Phe  Cys Ala Lys Asn Lys  Ser 
    1220                 1225     


<210>  2
<211>  1281
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CasM.21526

<400>  2

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


Thr Leu Arg Phe Glu Leu Lys Pro Ile Gly Lys Thr Leu Glu His Ile 
            20                  25                  30          


Lys Asn Ser Gly Ile Ile Glu Ser Asp Glu Thr Leu Glu Glu Gln Tyr 
        35                  40                  45              


Ala Ile Val Lys Asn Ile Ile Asp Lys Leu His Arg Lys His Ile Asp 
    50                  55                  60                  


Glu Ala Leu Ser Leu Val Asp Phe Thr Lys His Leu Asp Thr Leu Lys 
65                  70                  75                  80  


Thr Phe Gln Glu Leu Tyr Leu Lys Arg Gly Lys Thr Asp Lys Glu Lys 
                85                  90                  95      


Glu Glu Leu Glu Lys Leu Ser Ala Asp Leu Arg Lys Leu Ile Val Ser 
            100                 105                 110         


Tyr Leu Lys Gly Asn Val Lys Glu Lys Thr Gln His Asn Leu Asn Pro 
        115                 120                 125             


Ile Lys Glu Arg Phe Glu Ile Leu Phe Gly Lys Glu Leu Phe Thr Asn 
    130                 135                 140                 


Glu Glu Phe Phe Leu Leu Ala Glu Asn Glu Lys Glu Lys Lys Ala Ile 
145                 150                 155                 160 


Gln Ala Phe Lys Gly Phe Thr Thr Tyr Phe Lys Gly Phe Gln Glu Asn 
                165                 170                 175     


Arg Lys Asn Met Tyr Ser Glu Glu Gly Asn Ser Thr Ser Ile Ala Tyr 
            180                 185                 190         


Arg Ile Ile Asn Glu Asn Leu Pro Leu Phe Ile Glu Asn Ile Ala Arg 
        195                 200                 205             


Phe Gln Lys Val Met Ser Thr Ile Glu Lys Thr Thr Ile Lys Lys Leu 
    210                 215                 220                 


Glu Gln Asn Leu Lys Thr Glu Leu Lys Lys His Asn Leu Pro Gly Ile 
225                 230                 235                 240 


Phe Thr Ile Glu Tyr Phe Asn Asn Val Leu Thr Gln Glu Gly Ile Ser 
                245                 250                 255     


Arg Tyr Asn Thr Ile Ile Gly Gly Lys Thr Thr His Glu Gly Val Lys 
            260                 265                 270         


Ile Gln Gly Leu Asn Glu Ile Ile Asn Leu Tyr Asn Gln Gln Ser Lys 
        275                 280                 285             


Asp Val Lys Leu Pro Ile Leu Lys Pro Leu His Lys Gln Ile Leu Ser 
    290                 295                 300                 


Glu Glu Tyr Ser Thr Ser Phe Lys Ile Lys Ala Phe Glu Asn Asp Asn 
305                 310                 315                 320 


Glu Val Leu Lys Ala Ile Asp Thr Phe Trp Asn Glu His Ile Glu Lys 
                325                 330                 335     


Ser Ile His Pro Val Thr Gly Asn Lys Phe Asn Ile Leu Ser Lys Ile 
            340                 345                 350         


Glu Asn Leu Cys Asp Gln Leu Gln Lys Tyr Lys Asp Lys Asp Leu Glu 
        355                 360                 365             


Lys Leu Phe Ile Glu Arg Lys Asn Leu Ser Thr Val Ser His Gln Val 
    370                 375                 380                 


Tyr Gly Gln Trp Asn Ile Ile Arg Asp Ala Leu Arg Met His Leu Glu 
385                 390                 395                 400 


Met Asn Asn Lys Asn Ile Lys Glu Lys Asp Ile Asp Lys Tyr Leu Asp 
                405                 410                 415     


Asn Asp Ala Phe Ser Trp Lys Glu Ile Lys Asp Ser Ile Lys Ile Tyr 
            420                 425                 430         


Lys Glu His Val Glu Asp Ala Lys Glu Leu Asn Glu Asn Gly Ile Ile 
        435                 440                 445             


Lys Tyr Phe Ser Ala Met Ser Ile Asn Glu Glu Asp Asp Glu Lys Glu 
    450                 455                 460                 


Tyr Ser Ile Ser Leu Ile Lys Asn Ile Asn Glu Lys Tyr Asn Asn Val 
465                 470                 475                 480 


Lys Ser Ile Leu Gln Glu Asp Arg Thr Gly Lys Ser Asp Leu His Gln 
                485                 490                 495     


Asp Lys Glu Lys Val Gly Ile Ile Lys Glu Phe Leu Asp Ser Leu Lys 
            500                 505                 510         


Gln Leu Gln Trp Phe Leu Arg Leu Leu Tyr Val Thr Val Pro Leu Asp 
        515                 520                 525             


Glu Lys Asp Tyr Glu Phe Tyr Asn Glu Leu Glu Val Tyr Tyr Glu Ala 
    530                 535                 540                 


Leu Leu Pro Leu Asn Ser Leu Tyr Asn Lys Val Arg Asn Tyr Met Thr 
545                 550                 555                 560 


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


Thr Leu Leu Asp Gly Trp Asp Lys Asn Lys Glu Thr Ala Asn Leu Ser 
            580                 585                 590         


Ile Ile Leu Arg Lys Asn Gly Lys Tyr Tyr Leu Gly Ile Met Asn Lys 
        595                 600                 605             


Glu Asn Asn Thr Ile Phe Glu Tyr Tyr Pro Gly Thr Lys Ser Asn Asp 
    610                 615                 620                 


Tyr Tyr Glu Lys Met Ile Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met 
625                 630                 635                 640 


Leu Pro Lys Val Phe Phe Ser Lys Lys Gly Leu Glu Tyr Tyr Asn Pro 
                645                 650                 655     


Pro Lys Glu Ile Leu Asn Ile Tyr Glu Lys Gly Glu Phe Lys Lys Asp 
            660                 665                 670         


Lys Ser Gly Asn Phe Lys Lys Glu Ser Leu His Thr Leu Ile Asp Phe 
        675                 680                 685             


Tyr Lys Glu Ala Ile Ala Lys Asn Glu Asp Trp Glu Val Phe Asn Phe 
    690                 695                 700                 


Lys Phe Lys Asn Thr Lys Glu Tyr Glu Asp Ile Ser Gln Phe Tyr Arg 
705                 710                 715                 720 


Asp Val Glu Glu Gln Gly Tyr Leu Ile Thr Phe Glu Lys Val Asp Ala 
                725                 730                 735     


Asn Tyr Val Asp Lys Leu Val Lys Glu Gly Lys Leu Tyr Leu Phe Gln 
            740                 745                 750         


Ile Tyr Asn Lys Asp Phe Ser Glu Asn Lys Lys Ser Lys Gly Asn Pro 
        755                 760                 765             


Asn Leu His Thr Ile Tyr Trp Lys Gly Leu Tyr Asp Ser Glu Asn Leu 
    770                 775                 780                 


Lys Asn Val Val Tyr Lys Leu Asn Gly Glu Ala Glu Val Phe Tyr Arg 
785                 790                 795                 800 


Lys Lys Ser Ile Asp Tyr Pro Glu Glu Ile Tyr Asn His Gly His His 
                805                 810                 815     


Lys Glu Glu Leu Leu Gly Lys Phe Asn Tyr Pro Ile Ile Lys Asp Arg 
            820                 825                 830         


Arg Tyr Thr Gln Asp Lys Phe Leu Phe His Val Pro Ile Thr Met Asn 
        835                 840                 845             


Phe Ile Ser Lys Glu Glu Lys Arg Val Asn Gln Leu Ala Cys Glu Tyr 
    850                 855                 860                 


Leu Ser Ala Thr Lys Glu Asp Val His Ile Ile Gly Ile Asp Arg Gly 
865                 870                 875                 880 


Glu Arg His Leu Leu Tyr Leu Ser Leu Ile Asp Lys Glu Gly Asn Ile 
                885                 890                 895     


Lys Lys Gln Leu Ser Leu Asn Thr Ile Lys Asn Glu Asn Tyr Asp Lys 
            900                 905                 910         


Glu Ile Asp Tyr Arg Val Lys Leu Asp Glu Lys Glu Lys Lys Arg Asp 
        915                 920                 925             


Glu Ala Arg Lys Asn Trp Asp Val Ile Glu Asn Ile Lys Glu Leu Lys 
    930                 935                 940                 


Glu Gly Tyr Met Ser Gln Val Ile His Ile Ile Ala Lys Met Met Val 
945                 950                 955                 960 


Glu Glu Lys Ala Ile Leu Ile Met Glu Asp Leu Asn Ile Gly Phe Lys 
                965                 970                 975     


Arg Gly Arg Phe Lys Val Glu Lys Gln Val Tyr Gln Lys Phe Glu Lys 
            980                 985                 990         


Met Leu Ile Asp Lys Leu Asn Tyr  Leu Val Phe Lys Asn  Lys Asn Pro 
        995                 1000                 1005             


Leu Glu  Pro Gly Gly Ser Leu  Asn Ala Tyr Gln Leu  Thr Ser Lys 
    1010                 1015                 1020             


Phe Asp  Ser Phe Lys Lys Leu  Gly Lys Gln Ser Gly  Phe Ile Phe 
    1025                 1030                 1035             


Tyr Val  Pro Ser Ala Tyr Thr  Ser Lys Ile Asp Pro  Thr Thr Gly 
    1040                 1045                 1050             


Phe Tyr  Asn Phe Ile Gln Val  Asp Val Pro Asn Leu  Glu Lys Gly 
    1055                 1060                 1065             


Lys Glu  Phe Phe Ser Lys Phe  Glu Lys Ile Ile Tyr  Asn Thr Lys 
    1070                 1075                 1080             


Glu Asp  Tyr Phe Glu Phe His  Cys Lys Tyr Gly Lys  Phe Val Ser 
    1085                 1090                 1095             


Glu Pro  Lys Asn Lys Asp Asn  Asp Arg Lys Thr Lys  Glu Ser Leu 
    1100                 1105                 1110             


Thr Tyr  Tyr Asn Ala Ile Lys  Asp Thr Val Trp Val  Val Cys Ser 
    1115                 1120                 1125             


Thr Asn  His Glu Arg Tyr Lys  Ile Val Arg Asn Lys  Ala Gly Tyr 
    1130                 1135                 1140             


Tyr Glu  Ser His Pro Val Asp  Val Thr Lys Asn Leu  Lys Asp Ile 
    1145                 1150                 1155             


Phe Ser  Gln Ala Asn Ile Asn  Tyr Asn Glu Gly Lys  Asp Ile Lys 
    1160                 1165                 1170             


Pro Ile  Ile Ile Glu Ser Asn  Asn Ala Lys Leu Leu  Lys Ser Ile 
    1175                 1180                 1185             


Ala Glu  Gln Leu Lys Leu Ile  Leu Ala Met Arg Tyr  Asn Asn Gly 
    1190                 1195                 1200             


Lys His  Gly Asp Asp Glu Lys  Asp Tyr Ile Leu Ser  Pro Val Lys 
    1205                 1210                 1215             


Asn Lys  Gln Gly Lys Phe Phe  Cys Thr Leu Asp Gly  Asn Gln Thr 
    1220                 1225                 1230             


Leu Pro  Ile Asn Ala Asp Ala  Asn Gly Ala Tyr Asn  Ile Ala Leu 
    1235                 1240                 1245             


Lys Gly  Leu Leu Leu Ile Glu  Lys Ile Lys Lys Gln  Gln Gly Lys 
    1250                 1255                 1260             


Ile Lys  Asp Leu Tyr Ile Ser  Asn Leu Glu Trp Phe  Met Phe Met 
    1265                 1270                 1275             


Met Ser  Arg 
    1280     


<210>  3
<211>  1273
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CasM.21550

<400>  3

Met Gln Asp Lys Thr Gly Trp Ser Ser Phe Thr Asn Lys Tyr Ser Leu 
1               5                   10                  15      


Ser Lys Thr Leu Arg Phe Glu Leu Lys Pro Val Gly Asn Thr Gln Lys 
            20                  25                  30          


Met Leu Glu Asp Asp Gly Val Phe Gln Lys Asp Arg Glu Arg Gln Glu 
        35                  40                  45              


Asn Tyr Lys Lys Val Lys Pro Phe Met Asp Lys Leu His Arg Glu Phe 
    50                  55                  60                  


Ile Lys Glu Ala Leu Asn Asn Leu Lys Leu Glu Gly Leu Thr Glu Tyr 
65                  70                  75                  80  


Phe Glu Ile Phe Lys Lys Phe Arg Lys Asp Lys Asn Asn Lys Glu Leu 
                85                  90                  95      


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


Glu Thr Ala Gln Ile Trp Val Glu Lys Tyr Lys Glu Phe Gly Phe Lys 
        115                 120                 125             


Lys Lys Asn Ile Gly Phe Leu Phe Glu Glu Gly Val Phe Glu Leu Met 
    130                 135                 140                 


Lys Leu Lys Tyr Gly Asn Asp Glu Ala Ser Gln Ile Glu Lys Asn Gly 
145                 150                 155                 160 


Glu Val Leu Ser Ile Phe Asp Gly Trp Lys Gly Phe Leu Gly Tyr Phe 
                165                 170                 175     


Lys Lys Phe Phe Glu Thr Arg Asn Asn Phe Tyr Lys Asp Asp Gly Thr 
            180                 185                 190         


Ser Thr Ala Val Ser Thr Arg Ile Ile Asn Glu Asn Leu Lys Ile Tyr 
        195                 200                 205             


Leu Asp Asn Leu Ile Lys Tyr Asn Lys Ile Lys Asp Lys Val Asp Phe 
    210                 215                 220                 


Lys Glu Ala Asp Ile Leu Gln Glu Asn Lys Leu Asn Leu Ser Asp Phe 
225                 230                 235                 240 


Phe Asn Val Glu Ser Tyr Ala Lys Tyr Ser Leu Gln Lys Gly Ile Asp 
                245                 250                 255     


Tyr Tyr Asn Glu Ile Leu Gly Gly Lys Thr Leu Lys Asn Gly Thr Lys 
            260                 265                 270         


Leu Lys Gly Leu Asn Glu Val Ile Asn Glu Tyr Lys Gln Lys Asn Lys 
        275                 280                 285             


Ser Gly Glu Leu Ser Lys Phe Lys Met Leu Lys Lys Gln Ile Leu Gly 
    290                 295                 300                 


Glu Gly Glu Asp Arg Thr Leu Phe Glu Glu Ile Glu Asn Glu Asp Glu 
305                 310                 315                 320 


Leu Lys Asp Val Leu Lys Asp Phe Phe Tyr Asn Ala Asp Pro Lys Ile 
                325                 330                 335     


Thr Leu Phe Lys Thr Leu Leu Glu Asp Phe Phe Ser Asn Thr Glu Lys 
            340                 345                 350         


Tyr Lys Asp Glu Leu Asp Lys Ile Tyr Phe Asn Thr Val Ala Ile Asn 
        355                 360                 365             


Gly Ile Leu His Arg Trp Val Asp Asp Ser Gly Val Phe Gln Lys Tyr 
    370                 375                 380                 


Leu Phe Glu Val Leu Lys Ser Asn Lys Leu Val Lys Ser Asn His Tyr 
385                 390                 395                 400 


Asp Lys Lys Glu Asp Ser Tyr Lys Phe Pro Asp Phe Ile Ser Phe Glu 
                405                 410                 415     


His Ile Lys Val Ala Leu Glu Asn Cys Glu Arg Asp Gly Leu Lys Asp 
            420                 425                 430         


Lys Phe Trp Lys Glu Lys Tyr Tyr Thr Lys Glu Cys Leu Thr Glu Asn 
        435                 440                 445             


Gly Leu Ala Asn Leu Trp Gln Glu Phe Leu Glu Ile Tyr Lys Cys Glu 
    450                 455                 460                 


Phe Lys Lys Leu Tyr Asp Tyr Lys Thr Asp Asp Asn Asp Cys Tyr Leu 
465                 470                 475                 480 


Gln Tyr Arg Asp Asn Tyr Lys Lys Tyr Ile Leu Asp Ala Asn Phe Asn 
                485                 490                 495     


Pro Lys Glu Lys Ser Ala Lys Asp Ile Ile Lys Asp Tyr Leu Asp Ser 
            500                 505                 510         


Val Leu Ser Ile Tyr Gln Leu Ala Lys Tyr Phe Ala Leu Glu Lys Lys 
        515                 520                 525             


Lys Val Trp Thr Thr Asp Tyr Glu Thr Gly Asp Phe Tyr Tyr Glu Tyr 
    530                 535                 540                 


Ile Lys Phe Tyr Glu Asp Thr Tyr Glu Gln Ile Ile Lys Pro Tyr Asn 
545                 550                 555                 560 


Leu Val Arg Asn Tyr Leu Thr Arg Lys Pro Ile Asn Thr Ala Lys Lys 
                565                 570                 575     


Trp Lys Leu Asn Phe Asp Asn Ala Tyr Leu Ala Ser Gly Trp Asp Lys 
            580                 585                 590         


Asp Lys Glu Val Ser Asn Leu Thr Val Ile Leu Arg Arg Asp Glu Gln 
        595                 600                 605             


Tyr Tyr Leu Ala Ile Met Lys Lys Gly Lys Asn Lys Ile Phe Glu Lys 
    610                 615                 620                 


Lys Phe Ser Cys Gly Glu Phe Glu Lys Met Glu Tyr Lys Gln Ile Ala 
625                 630                 635                 640 


Glu Ala Ser Ser Asp Ile His Asn Leu Val Leu Met Asn Asp Gly Ser 
                645                 650                 655     


Cys Arg Arg Cys Ile Lys Met His Asp Lys Arg Lys Tyr Trp Pro Leu 
            660                 665                 670         


Asp Ile Ser Ile Ile Lys Glu Lys Lys Ser Tyr Ala Lys Glu Asn Phe 
        675                 680                 685             


Val Arg Arg Asp Phe Glu Arg Phe Val Asn Tyr Met Lys Lys Cys Ser 
    690                 695                 700                 


Leu Leu Tyr Trp Lys Glu Tyr Asp Leu Lys Phe Ser Asp Thr Ser Thr 
705                 710                 715                 720 


Tyr Lys Asn Ile Asn Asp Phe Thr Asn Glu Ile Ala Ser Gln Gly Tyr 
                725                 730                 735     


Lys Leu Ser Phe Ser Ala Ile Pro Glu Ser Tyr Ile Asn Glu Lys Asn 
            740                 745                 750         


Asn Asn Gly Glu Leu Tyr Leu Phe Gln Ile Tyr Asn Lys Asp Phe Gly 
        755                 760                 765             


Ile Lys Thr Glu Gly Asn Lys Asn Leu His Thr Met Tyr Trp Glu Ser 
    770                 775                 780                 


Ile Phe Ser Glu Glu Asn Arg Phe Arg Asn Phe Ile Val Lys Leu Asn 
785                 790                 795                 800 


Gly Lys Ala Glu Ile Phe Tyr Arg Pro Lys Ser Glu Gln Val Glu Lys 
                805                 810                 815     


Glu Gln Arg Asn Phe Thr Arg Glu Ile Ile Lys Asn Arg Arg Tyr Thr 
            820                 825                 830         


Glu Asn Lys Ile Tyr Phe His Cys Pro Ile Thr Leu Asn Arg Ile Ser 
        835                 840                 845             


Arg Glu Asn Val Lys Lys Phe Asn Asn Gly Ile Asn Asn Tyr Ile Ala 
    850                 855                 860                 


Thr Asn Pro Asn Ile Asn Ile Leu Gly Val Asp Arg Gly Glu Lys His 
865                 870                 875                 880 


Leu Val Tyr Tyr Ala Ile Val Asp Gln Asp Gly Lys Leu Ile Asp Ala 
                885                 890                 895     


Glu Asp Ala Thr Gly Ser Phe Asn Thr Ile Gly Ser Thr Asp Tyr His 
            900                 905                 910         


Arg Leu Leu Glu Glu Lys Ala Lys Asp Arg Glu Lys Glu Arg Lys Asp 
        915                 920                 925             


Trp Asp Leu Ile Arg Gly Ile Lys Asp Leu Lys Lys Gly Tyr Ile Ser 
    930                 935                 940                 


Leu Val Val Arg Lys Ile Ala Asp Leu Ala Ile Lys Tyr Asn Ala Ile 
945                 950                 955                 960 


Ile Ile Phe Glu Asp Leu Asn Thr Arg Phe Lys Gln Ile Arg Gly Gly 
                965                 970                 975     


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


Leu Ser Phe Leu Val Asn Lys Gly  Glu Lys Asp Pro Glu  Gln Ala Gly 
        995                 1000                 1005             


His Leu  Leu Lys Ala Tyr Gln  Leu Ala Ala Pro Phe  Gln Thr Phe 
    1010                 1015                 1020             


Asp Lys  Met Gly Arg Gln Thr  Gly Ile Ile Phe Tyr  Thr Gln Ala 
    1025                 1030                 1035             


Ser Tyr  Thr Ser Lys Ile Asp  Pro Ile Thr Gly Trp  Arg Pro Asn 
    1040                 1045                 1050             


Leu Tyr  Leu Lys Tyr Arg Asn  Ile Asp Asp Ser Lys  Glu Ser Ile 
    1055                 1060                 1065             


Lys Lys  Phe Lys Ser Ile Leu  Phe Asn Lys Glu Lys  Asn Arg Phe 
    1070                 1075                 1080             


Glu Phe  Thr Tyr Asp Leu Lys  Asp Phe Val Asp Phe  Glu Glu Asp 
    1085                 1090                 1095             


Lys Ile  Pro Glu Lys Thr Glu  Trp Thr Leu Cys Ser  Ser Val Glu 
    1100                 1105                 1110             


Arg His  Lys Trp Asn Arg His  Met Asn Asn Asn Lys  Gly Gly Tyr 
    1115                 1120                 1125             


Glu Val  Tyr Lys Asp Leu Thr  Glu Asn Phe Tyr Lys  Leu Phe Asp 
    1130                 1135                 1140             


Glu Asn  Asn Ile Ser Met Asn  Lys Asp Ile Val Asp  Gln Val Glu 
    1145                 1150                 1155             


Ser Ile  Ser Asn Gly Asn Phe  Phe Arg Gln Phe Ile  Tyr Leu Phe 
    1160                 1165                 1170             


Asn Leu  Val Cys Gln Ile Arg  Asn Thr Asp Glu Lys  Ala Glu Asp 
    1175                 1180                 1185             


Val Asp  Lys Arg Asp Phe Ile  Leu Ser Pro Val Glu  Pro Phe Phe 
    1190                 1195                 1200             


Asp Ser  Arg Arg Ala Lys Asp  Phe Lys Ala Tyr Gly  Asp Asn Leu 
    1205                 1210                 1215             


Pro Lys  Asn Gly Asp Glu Asn  Gly Ala Tyr Asn Ile  Ala Arg Lys 
    1220                 1225                 1230             


Gly Val  Leu Ile Ile Lys Lys  Ile Lys Glu Tyr Tyr  Asn Gln Asn 
    1235                 1240                 1245             


Gly Ser  Cys Asp Lys Leu Gly  Trp Gly Asp Leu Ser  Ile Ser His 
    1250                 1255                 1260             


Lys Glu  Trp Asp Asp Phe Ala  Thr Asn Asn 
    1265                 1270             


<210>  4
<211>  1467
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CasM.21530

<400>  4

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


Arg Phe Glu Leu Val Pro Gln Gly Lys Thr Asn Asp Tyr Ile Asp Lys 
            20                  25                  30          


Trp Ile Lys Glu Leu Glu Leu Glu Asn Lys His Glu Val Leu Lys Asp 
        35                  40                  45              


Lys Val Asp Glu Thr Ile Ala Lys Tyr Ile Glu Asn Ile Lys Asp Lys 
    50                  55                  60                  


Leu Asn Glu Ser Asn Tyr Glu Pro Glu Thr Lys Ser Lys Ile Ile Gln 
65                  70                  75                  80  


Cys Ile Glu Asn Ser Lys Ser Lys Ile Asn Tyr Thr Asp Leu Lys Glu 
                85                  90                  95      


Asn Ser Val Arg Glu Val Val Ser Ile Trp Phe Lys Glu Ile Asn Asn 
            100                 105                 110         


Glu Leu Asn Glu Val Asp Leu Arg Lys Asn Ile Lys Asn Lys Ile Asn 
        115                 120                 125             


Asn Arg Ile Lys Lys Leu Ser Glu Ile Val Glu Asp Glu Leu Lys Asn 
    130                 135                 140                 


Ile Ile Leu Glu Asp Lys Asn Arg Ala Lys Lys Tyr Glu Lys Val Lys 
145                 150                 155                 160 


Lys Ile Leu Asp Glu Tyr His Lys Asp Phe Ile Glu Arg Val Leu Lys 
                165                 170                 175     


Asn Leu Asp Gln Thr Asp Phe Asn Lys Leu Leu Lys Glu Tyr Leu Asp 
            180                 185                 190         


Leu Tyr Thr Lys Lys Lys Asp Lys Lys Glu Thr Lys Glu Phe Val Lys 
        195                 200                 205             


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


Pro Asp Tyr Lys Ile Leu Asp Lys Asp Lys Leu Phe Lys Arg Gly Lys 
225                 230                 235                 240 


Lys Ser Glu Lys Lys Asp Ser Ser His Glu Glu Asn Asp Asp Thr Asn 
                245                 250                 255     


Val Gly Gly Ile Leu Glu Lys Phe Leu Glu Glu Asn Ser Thr Leu Lys 
            260                 265                 270         


His Lys Leu Glu Glu Ser Leu Arg Asn Asn Glu Asp Glu Thr Ile Asp 
        275                 280                 285             


Leu Phe Glu Leu Leu Arg Ser Phe Glu Gly Phe Thr Thr Tyr Phe Arg 
    290                 295                 300                 


Asn Phe His Lys Asn Arg Glu Asn Leu Tyr Ser Asp Glu Asp Lys Phe 
305                 310                 315                 320 


Ser Thr Ile Ala His Arg Leu Ile His Glu Asn Leu Pro Lys Phe Ile 
                325                 330                 335     


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


Glu Glu Ile Gln Lys Gln Leu Gly Ile Thr Glu Ser Leu Asp Asp Val 
        355                 360                 365             


Phe Ser Ile Glu Tyr Phe Thr Lys Cys Leu Thr Gln Ser Gly Ile Asp 
    370                 375                 380                 


Arg Tyr Asn Tyr Ile Leu Gly Gly Lys Ser Val Glu Asn Gly Gln Asn 
385                 390                 395                 400 


Ile Arg Gly Val Asn Ser Phe Ile Asn Asn Glu Ile Asn Gln Ser Val 
                405                 410                 415     


Ser Glu Lys Lys Asp Arg Val Pro Val Met Lys Met Leu Tyr Lys Leu 
            420                 425                 430         


Pro Leu Phe Asp Arg Thr Ser Ser Ser Phe Arg Tyr Asp Pro Ile Glu 
        435                 440                 445             


Asn Asp Gln Asp Leu Ile Glu Arg Ile Val Ser Phe Tyr Glu Arg Asn 
    450                 455                 460                 


Leu Thr Gln Tyr Ile Asp Thr Thr Thr Ser Asp Asp Thr Pro Val Asn 
465                 470                 475                 480 


Ile Leu Glu Met Ile Lys Glu Leu Leu Gln Asn Ile His Asn Tyr Arg 
                485                 490                 495     


Glu Gly Leu Tyr Val Asn Gly Gly Thr Thr Leu Thr Gln Ile Ser Gln 
            500                 505                 510         


Lys Ile Phe Gly Asp Trp Arg Tyr Ile His Asp Val Leu Ser Tyr Tyr 
        515                 520                 525             


Tyr Asp Thr Ile Ile Ser Pro Leu Lys Lys Asp Lys Lys Gly Asn Leu 
    530                 535                 540                 


Lys Ser Arg Leu Gly Thr Glu Glu Lys Gln Lys Glu Lys Trp Met Lys 
545                 550                 555                 560 


Gln Lys Gln Phe Ser Val Val Leu Ile Glu Lys Ala Leu Asn Glu Tyr 
                565                 570                 575     


Lys Lys Val Glu Thr Asn Glu Glu Leu Lys Asn Lys Ile Thr Asp Thr 
            580                 585                 590         


Thr Leu Cys Asp Phe Phe Ala Arg Cys Gly Thr Asp Lys Asp Gly Lys 
        595                 600                 605             


Asp Leu Phe Lys Arg Ile Asp Glu Lys Leu Thr Glu Lys Asn Ser His 
    610                 615                 620                 


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


Lys Leu Met Gln Asn Glu Ser Arg Ile Ser Leu Ile Lys Asn Phe Leu 
                645                 650                 655     


Asp Ala Ile Leu Gly Asp Lys Glu Asp Ile Thr Ala Gly Leu Leu His 
            660                 665                 670         


Phe Ile Lys Pro Leu Ile Pro Arg Glu Glu Val Ala Asp Lys Asn Glu 
        675                 680                 685             


Leu Phe Tyr Ser Glu Phe Glu Arg Tyr Tyr Asn Leu Leu Ser Glu Ile 
    690                 695                 700                 


Ile Pro Leu Tyr Asn Lys Val Arg Asn Tyr Leu Thr Gln Lys Pro Phe 
705                 710                 715                 720 


Ser Ile Glu Lys Ile Lys Leu Asn Phe Glu Asn Pro Met Leu Leu Ala 
                725                 730                 735     


Gly Trp Asp Val Asn Lys Glu Ala Asp Asn Ser Cys Val Leu Phe Arg 
            740                 745                 750         


Lys Asn Gly Phe Tyr Tyr Leu Gly Ile Met Asn Lys Tyr Tyr Arg Asp 
        755                 760                 765             


Val Phe Lys Asn Tyr Glu Thr Ala Asn Asp Gly Glu Asp Phe Tyr Glu 
    770                 775                 780                 


Lys Met Val Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu Pro Lys 
785                 790                 795                 800 


Val Phe Phe Ser Glu Lys Asn Ile Gly Tyr Phe Asn Pro Ser Asp Glu 
                805                 810                 815     


Ile Leu Arg Ile Arg Asn Thr Ala Ser Tyr Ser Lys Asn Gly Lys Pro 
            820                 825                 830         


Arg Glu Gly Tyr Lys Lys Ala Asp Phe Ser Val Asn Asp Cys Gln Gln 
        835                 840                 845             


Leu Ile Asp Phe Phe Lys Glu Ser Ile Leu Lys His Glu Asp Trp Ser 
    850                 855                 860                 


Lys Phe Asn Phe Gln Phe Lys Pro Thr Ser Arg Tyr Asn Asp Ile Ser 
865                 870                 875                 880 


Glu Phe Tyr Lys Asp Val Lys Asn Gln Gly Tyr Lys Ile Asn Phe Val 
                885                 890                 895     


Lys Ile Pro Ser Thr Tyr Ile Asn Gln Leu Val Gln Glu Gly Lys Leu 
            900                 905                 910         


Tyr Leu Phe Lys Ile His Asn Lys Asp Phe Ser Glu Lys Lys Lys Pro 
        915                 920                 925             


Gly Gly Lys Asp Asn Leu His Thr Leu Tyr Trp Lys Met Leu Phe Ser 
    930                 935                 940                 


Glu Glu Asn Leu Lys Asp Val Val Phe Lys Leu Asp Gly Glu Ala Glu 
945                 950                 955                 960 


Ile Phe Phe Arg Pro Lys Ser Ile Ile Tyr Asp Glu Asn Ile Trp Lys 
                965                 970                 975     


Asn Gly His His Asn Glu Lys Leu Lys Asp Lys Phe Asn Tyr Pro Ile 
            980                 985                 990         


Ile Lys Asp Arg Arg Phe Ala Leu  Asp Lys Ile Tyr Phe  His Val Pro 
        995                 1000                 1005             


Ile Thr  Ile Asn Phe Lys Ala  Gly Asp Val Pro Asp  Asn Glu Asp 
    1010                 1015                 1020             


Glu Glu  Lys Asn Asn Gln Gln  Asn Glu Met Lys Asn  Glu Ser Phe 
    1025                 1030                 1035             


Asn Gln  Lys Ile Leu Ser Phe  Leu Lys Asp Arg Asp  Asp Val His 
    1040                 1045                 1050             


Ile Ile  Gly Ile Asp Arg Gly  Glu Arg His Leu Leu  Tyr Val Val 
    1055                 1060                 1065             


Val Ile  Asn Ser Asp Gly Lys  Ile Val Glu Gln Phe  Ser Leu Asn 
    1070                 1075                 1080             


Lys Ile  Pro Arg Glu Lys Ser  Asp Val Pro Ile Asp  Tyr Leu Asp 
    1085                 1090                 1095             


Arg Leu  Asn Asn Lys Glu Gly  Gln Leu Asp Glu Ala  Arg Lys Asn 
    1100                 1105                 1110             


Trp Gln  Thr Ile Gln Asn Ile  Lys Glu Leu Lys Glu  Gly Tyr Leu 
    1115                 1120                 1125             


Ser His  Val Ile His Ile Ile  Thr Arg Leu Ile Val  Lys Tyr Asn 
    1130                 1135                 1140             


Ala Ile  Val Val Met Glu Asp  Leu Asn Ser Gly Phe  Lys Arg Gly 
    1145                 1150                 1155             


Arg Gln  Lys Val Glu Lys Gln  Val Tyr Gln Lys Phe  Glu Lys Met 
    1160                 1165                 1170             


Leu Ile  Asn Lys Leu Asn Tyr  Leu Val Phe Lys Asp  Lys Lys Ala 
    1175                 1180                 1185             


Gly Glu  Pro Gly Gly Val Leu  Lys Gly Leu Gln Leu  Thr Asp Lys 
    1190                 1195                 1200             


Phe Glu  Ser Phe Lys Asn Leu  Gly Lys Gln Ser Gly  Ile Ile Phe 
    1205                 1210                 1215             


Tyr Val  Pro Pro Ala Tyr Thr  Ser Ala Ile Asp Pro  Val Thr Gly 
    1220                 1225                 1230             


Tyr Val  Gln Tyr Leu Tyr Pro  Leu Lys Arg Ala Asp  Ser Ile Glu 
    1235                 1240                 1245             


Lys Ala  Lys Asn Phe Tyr Ser  Lys Phe Asp Ser Thr  Lys Tyr Asn 
    1250                 1255                 1260             


Ala Glu  Lys Asp Arg Phe Glu  Phe Thr Phe Asp Tyr  Glu Lys Ile 
    1265                 1270                 1275             


Pro Asn  Thr Arg Tyr Glu Gly  Lys Ser Gln Trp Thr  Ile Cys Thr 
    1280                 1285                 1290             


Ser Asp  Glu Glu Arg Tyr Tyr  Trp Asp Lys Ser Leu  Asn Asn Gly 
    1295                 1300                 1305             


Lys Gly  Gly Gln Lys Glu Tyr  Lys Thr Thr Ser Glu  Met Lys Gln 
    1310                 1315                 1320             


Leu Phe  Lys Glu Ala Ala Ile  Pro Tyr His Thr Gly  Glu Glu Leu 
    1325                 1330                 1335             


Lys Gln  Tyr Ile Ala Gly Ile  Ser Gly Asn Pro Glu  Lys Lys Ile 
    1340                 1345                 1350             


Lys Asp  Lys Glu Phe Phe Asn  Arg Leu Asn Leu Leu  Leu His Val 
    1355                 1360                 1365             


Thr Leu  Lys Leu Arg His Asn  Asn Gly Lys Asp Gly  Asp Lys Glu 
    1370                 1375                 1380             


Gln Asp  Tyr Ile Leu Ser Pro  Val Glu Pro Phe Phe  Asp Ser Arg 
    1385                 1390                 1395             


Lys Ala  Lys Gly Asp Leu Pro  Glu Asn Ala Asp Ala  Asn Gly Ala 
    1400                 1405                 1410             


Phe Asn  Ile Ala Arg Lys Gly  Leu Val Leu Leu Lys  Arg Leu Lys 
    1415                 1420                 1425             


Lys Met  Asp Ile Asp Glu Phe  Glu Lys Thr Lys Lys  Ser Lys Asp 
    1430                 1435                 1440             


Gly Lys  Ser Gln Trp Leu Pro  His Lys Glu Trp Leu  Glu Phe Ser 
    1445                 1450                 1455             


Gln Glu  Lys His Ala Ala Val  Leu Asn 
    1460                 1465         


<210>  5
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  nuclear localization signal

<400>  5

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


Glu Phe 
        


<210>  6
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  endosomal escape peptide


<220>
<221>  SITE
<222>  (4)..(4)
<223>  Xaa is lysine, histidine, or arginine

<220>
<221>  SITE
<222>  (8)..(8)
<223>  Xaa is lysine, histidine, or arginine

<220>
<221>  SITE
<222>  (11)..(11)
<223>  Xaa is lysine, histidine, or arginine

<220>
<221>  SITE
<222>  (15)..(15)
<223>  Xaa is lysine, histidine, or arginine

<220>
<221>  SITE
<222>  (19)..(19)
<223>  Xaa is lysine, histidine, or arginine

<400>  6

Gly Leu Phe Xaa Ala Leu Leu Xaa Leu Leu Xaa Ser Leu Trp Xaa Leu 
1               5                   10                  15      


Leu Leu Xaa Ala 
            20  


<210>  7
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  endosomal escape peptide

<400>  7

Gly Leu Phe His Ala Leu Leu His Leu Leu His Ser Leu Trp His Leu 
1               5                   10                  15      


Leu Leu His Ala 
            20  


<210>  8
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker


<220>
<221>  SITE
<222>  (2)..(10)
<223>  individual amino acid residues may be present or absent

<400>  8

Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly 
1               5                   10  


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

<220>
<223>  linker


<220>
<221>  SITE
<222>  (3)..(4)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (5)..(6)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (7)..(8)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (9)..(10)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (11)..(12)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (13)..(14)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (15)..(16)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (17)..(18)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (19)..(20)
<223>  grouped amino acid residues may be present or absent

<400>  9

Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser 
1               5                   10                  15      


Gly Ser Gly Ser 
            20  


<210>  10
<211>  50
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker


<220>
<221>  SITE
<222>  (6)..(10)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (11)..(15)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (16)..(20)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (21)..(25)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (26)..(30)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (31)..(35)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (36)..(40)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (41)..(45)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (46)..(50)
<223>  grouped amino acid residues may be present or absent

<400>  10

Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly 
1               5                   10                  15      


Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Ser 
            20                  25                  30          


Gly Gly Ser Gly Ser Gly Gly Ser Gly Ser Gly Gly Ser Gly Ser Gly 
        35                  40                  45              


Gly Ser 
    50  


<210>  11
<211>  60
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker


<220>
<221>  SITE
<222>  (7)..(12)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (13)..(18)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (19)..(24)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (25)..(30)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (31)..(36)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (37)..(42)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (43)..(48)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (49)..(54)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (55)..(60)
<223>  grouped amino acid residues may be present or absent

<400>  11

Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
1               5                   10                  15      


Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly 
            20                  25                  30          


Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser 
        35                  40                  45              


Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser 
    50                  55                  60  


<210>  12
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker


<220>
<221>  SITE
<222>  (5)..(8)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (9)..(12)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (13)..(16)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (17)..(20)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (21)..(24)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (25)..(28)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (29)..(32)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (33)..(36)
<223>  grouped amino acid residues may be present or absent

<220>
<221>  SITE
<222>  (37)..(40)
<223>  grouped amino acid residues may be present or absent

<400>  12

Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser 
1               5                   10                  15      


Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser 
            20                  25                  30          


Gly Gly Gly Ser Gly Gly Gly Ser 
        35                  40  


<210>  13
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker

<400>  13

Gly Gly Ser Gly 
1               


<210>  14
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker

<400>  14

Gly Gly Ser Gly Gly 
1               5   


<210>  15
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker

<400>  15

Gly Ser Gly Ser Gly 
1               5   


<210>  16
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker

<400>  16

Gly Ser Gly Gly Gly 
1               5   


<210>  17
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker

<400>  17

Gly Gly Gly Ser Gly 
1               5   


<210>  18
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker

<400>  18

Gly Ser Ser Ser Gly 
1               5   


<210>  19
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  crRNA

<400>  19
agauuucuac uuuuguagau uauuaaauac ucguauugcu                             40


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

<220>
<223>  crRNA

<400>  20
gaauuucuac uauuguagau uauuaaauac ucguauugcu                             40


<210>  21
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  crRNA

<400>  21
agauuucuac uauuguagau uauuaaauac ucguauugcu                             40


<210>  22
<211>  5
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  ss nucleic acid in a reporter

<400>  22
uuuuu                                                                    5


<210>  23
<211>  8
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  ss nucleic acid in a reporter

<400>  23
uuuuuuuu                                                                 8


<210>  24
<211>  10
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  ss nucleic acid in a reporter

<400>  24
uuuuuuuuuu                                                              10


<210>  25
<211>  10
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  ss nucleic acid in a reporter


<220>
<221>  misc_feature
<222>  (5)..(6)
<223>  ribonucleotides

<400>  25
ttttuutttt                                                              10


<210>  26
<211>  6
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  ss nucleic acid in a reporter


<220>
<221>  misc_feature
<222>  (3)..(4)
<223>  ribonucleotides

<400>  26
ttuutt                                                                   6


<210>  27
<211>  6
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter


<220>
<221>  misc_feature
<222>  (3)..(4)
<223>  ribonucleotides

<400>  27
taaugc                                                                   6


<210>  28
<211>  6
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter


<220>
<221>  misc_feature
<222>  (3)..(4)
<223>  ribonucleotides

<400>  28
tauggc                                                                   6


<210>  29
<211>  5
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter

<400>  29
uuuuu                                                                    5


<210>  30
<211>  8
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter

<400>  30
ttattatt                                                                 8


<210>  31
<211>  6
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter

<400>  31
tttttt                                                                   6


<210>  32
<211>  8
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter

<400>  32
tttttttt                                                                 8


<210>  33
<211>  10
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter

<400>  33
tttttttttt                                                              10


<210>  34
<211>  12
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter

<400>  34
tttttttttt tt                                                           12


<210>  35
<211>  14
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter

<400>  35
tttttttttt tttt                                                         14


<210>  36
<211>  6
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter

<400>  36
aaaaaa                                                                   6


<210>  37
<211>  6
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter

<400>  37
cccccc                                                                   6


<210>  38
<211>  6
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter

<400>  38
gggggg                                                                   6


<210>  39
<211>  8
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  single stranded nucleic acid in a reporter

<400>  39
ttattatt                                                                 8


<210>  40
<211>  1224
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cas12 variant

<400>  40

Met Lys Lys Ile Asp Asn Phe Val Gly Cys Tyr Pro Val Ser Lys Thr 
1               5                   10                  15      


Leu Arg Phe Lys Ala Ile Pro Ile Gly Lys Thr Gln Glu Asn Ile Glu 
            20                  25                  30          


Lys Lys Arg Leu Val Glu Glu Asp Glu Val Arg Ala Lys Asp Tyr Lys 
        35                  40                  45              


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


Val Leu Asp Asn Val Lys Leu Asp Gly Leu Glu Glu Tyr Tyr Met Leu 
65                  70                  75                  80  


Phe Asn Lys Ser Asp Arg Glu Glu Ser Asp Asn Lys Lys Ile Glu Ile 
                85                  90                  95      


Met Glu Glu Arg Phe Arg Arg Val Ile Ser Lys Ser Phe Lys Asn Asn 
            100                 105                 110         


Glu Glu Tyr Lys Lys Ile Phe Ser Lys Lys Ile Ile Glu Glu Ile Leu 
        115                 120                 125             


Pro Asn Tyr Ile Lys Asp Glu Glu Glu Lys Glu Leu Val Lys Gly Phe 
    130                 135                 140                 


Lys Gly Phe Tyr Thr Ala Phe Val Gly Tyr Ala Gln Asn Arg Glu Asn 
145                 150                 155                 160 


Met Tyr Ser Asp Glu Lys Lys Ser Thr Ala Ile Ser Tyr Arg Ile Val 
                165                 170                 175     


Asn Glu Asn Met Pro Arg Phe Ile Thr Asn Ile Lys Val Phe Glu Lys 
            180                 185                 190         


Ala Lys Ser Ile Leu Asp Val Asp Lys Ile Asn Glu Ile Asn Glu Tyr 
        195                 200                 205             


Ile Leu Asn Asn Asp Tyr Tyr Val Asp Asp Phe Phe Asn Ile Asp Phe 
    210                 215                 220                 


Phe Asn Tyr Val Leu Asn Gln Lys Gly Ile Asp Ile Tyr Asn Ala Ile 
225                 230                 235                 240 


Ile Gly Gly Ile Val Thr Gly Asp Gly Arg Lys Ile Gln Gly Leu Asn 
                245                 250                 255     


Glu Cys Ile Asn Leu Tyr Asn Gln Glu Asn Lys Lys Ile Arg Leu Pro 
            260                 265                 270         


Gln Phe Lys Pro Leu Tyr Lys Gln Ile Leu Ser Glu Ser Glu Ser Met 
        275                 280                 285             


Ser Phe Tyr Ile Asp Glu Ile Glu Ser Asp Asp Met Leu Ile Asp Met 
    290                 295                 300                 


Leu Lys Glu Ser Leu Gln Ile Asp Ser Thr Ile Asn Asn Ala Ile Asp 
305                 310                 315                 320 


Asp Leu Lys Val Leu Phe Asn Asn Ile Phe Asp Tyr Asp Leu Ser Gly 
                325                 330                 335     


Ile Phe Ile Asn Asn Gly Leu Pro Ile Thr Thr Ile Ser Asn Asp Val 
            340                 345                 350         


Tyr Gly Gln Trp Ser Thr Ile Ser Asp Gly Trp Asn Glu Arg Tyr Asp 
        355                 360                 365             


Val Leu Ser Asn Ala Lys Asp Lys Glu Ser Glu Lys Tyr Phe Glu Lys 
    370                 375                 380                 


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


Gln Glu Leu Gly Gly Lys Asp Leu Ser Ile Cys Lys Lys Ile Asn Glu 
                405                 410                 415     


Ile Ile Ser Glu Met Ile Asp Asp Tyr Lys Ser Lys Ile Glu Glu Ile 
            420                 425                 430         


Gln Tyr Leu Phe Asp Ile Lys Glu Leu Glu Lys Pro Leu Val Thr Asp 
        435                 440                 445             


Leu Asn Lys Ile Glu Leu Ile Lys Asn Ser Leu Asp Gly Leu Lys Arg 
    450                 455                 460                 


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


Arg Asp Glu Val Phe Tyr Gly Tyr Phe Ile Lys Cys Ile Asp Ala Ile 
                485                 490                 495     


Lys Glu Ile Asp Gly Val Tyr Asn Lys Thr Arg Asn Tyr Leu Thr Lys 
            500                 505                 510         


Lys Pro Tyr Ser Lys Asp Lys Phe Lys Leu Tyr Phe Glu Asn Pro Gln 
        515                 520                 525             


Leu Met Gly Gly Trp Asp Arg Asn Lys Glu Ser Asp Tyr Arg Ser Thr 
    530                 535                 540                 


Leu Leu Arg Lys Asn Gly Lys Tyr Tyr Val Ala Ile Ile Asp Lys Ser 
545                 550                 555                 560 


Ser Ser Asn Cys Met Met Asn Ile Glu Glu Asp Glu Asn Asp Asn Tyr 
                565                 570                 575     


Glu Lys Ile Asn Tyr Lys Leu Leu Pro Gly Pro Asn Lys Met Leu Pro 
            580                 585                 590         


Lys Val Phe Phe Ser Lys Lys Asn Arg Glu Tyr Phe Ala Pro Ser Lys 
        595                 600                 605             


Glu Ile Glu Arg Ile Tyr Ser Thr Gly Thr Phe Lys Lys Asp Thr Asn 
    610                 615                 620                 


Phe Val Lys Lys Asp Cys Glu Asn Leu Ile Thr Phe Tyr Lys Asp Ser 
625                 630                 635                 640 


Leu Asp Arg His Glu Asp Trp Ser Lys Ser Phe Asp Phe Ser Phe Lys 
                645                 650                 655     


Glu Ser Ser Ala Tyr Arg Asp Ile Ser Glu Phe Tyr Arg Asp Val Glu 
            660                 665                 670         


Lys Gln Gly Tyr Arg Val Ser Phe Asp Leu Leu Ser Ser Asn Ala Val 
        675                 680                 685             


Asn Thr Leu Val Glu Glu Gly Lys Leu Tyr Leu Phe Gln Leu Tyr Asn 
    690                 695                 700                 


Lys Asp Phe Ser Glu Lys Ser His Gly Ile Pro Asn Leu His Thr Met 
705                 710                 715                 720 


Tyr Phe Arg Ser Leu Phe Asp Asp Asn Asn Lys Gly Asn Ile Arg Leu 
                725                 730                 735     


Asn Gly Gly Ala Glu Met Phe Met Arg Arg Ala Ser Leu Asn Lys Gln 
            740                 745                 750         


Asp Val Thr Val His Lys Ala Asn Gln Pro Ile Lys Asn Lys Asn Leu 
        755                 760                 765             


Leu Asn Pro Lys Lys Thr Thr Thr Leu Pro Tyr Asp Val Tyr Lys Asp 
    770                 775                 780                 


Lys Arg Phe Thr Glu Asp Gln Tyr Glu Val His Ile Pro Ile Thr Met 
785                 790                 795                 800 


Asn Lys Val Pro Asn Asn Pro Tyr Lys Ile Asn His Met Val Arg Glu 
                805                 810                 815     


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


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


Val Glu Gln Leu Ser Leu Asn Glu Ile Ile Asn Glu Asn Asn Gly Ile 
    850                 855                 860                 


Ser Ile Arg Thr Asp Tyr His Thr Leu Leu Asp Ala Lys Glu Arg Glu 
865                 870                 875                 880 


Arg Asp Glu Ser Arg Lys Gln Trp Lys Gln Ile Glu Asn Ile Lys Glu 
                885                 890                 895     


Leu Lys Glu Gly Tyr Ile Ser Gln Val Val His Lys Ile Cys Glu Leu 
            900                 905                 910         


Val Glu Lys Tyr Asp Ala Val Ile Ala Leu Glu Asp Leu Asn Ser Gly 
        915                 920                 925             


Phe Lys Asn Ser Arg Val Lys Val Glu Lys Gln Val Tyr Gln Lys Phe 
    930                 935                 940                 


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


Asp Tyr Asn Lys Pro Gly Gly Val Leu Asn Gly Tyr Gln Leu Thr Thr 
                965                 970                 975     


Gln Phe Glu Ser Phe Ser Lys Met Gly Thr Gln Asn Gly Ile Met Phe 
            980                 985                 990         


Tyr Ile Pro Ala Trp Leu Thr Ser  Lys Met Asp Pro Thr  Thr Gly Phe 
        995                 1000                 1005             


Val Asp  Leu Leu Lys Pro Lys  Tyr Lys Asn Lys Ala  Asp Ala Gln 
    1010                 1015                 1020             


Lys Phe  Phe Ser Gln Phe Asp  Ser Ile Arg Tyr Asp  Asn Gln Glu 
    1025                 1030                 1035             


Asp Ala  Phe Val Phe Lys Val  Asn Tyr Thr Lys Phe  Pro Arg Thr 
    1040                 1045                 1050             


Asp Ala  Asp Tyr Asn Lys Glu  Trp Glu Ile Tyr Thr  Asn Gly Glu 
    1055                 1060                 1065             


Arg Ile  Arg Val Phe Arg Asn  Pro Lys Lys Asn Asn  Glu Tyr Asp 
    1070                 1075                 1080             


Tyr Glu  Thr Val Asn Val Ser  Glu Arg Met Lys Glu  Leu Phe Asp 
    1085                 1090                 1095             


Ser Tyr  Asp Leu Leu Tyr Asp  Lys Gly Glu Leu Lys  Glu Thr Ile 
    1100                 1105                 1110             


Cys Glu  Met Glu Glu Ser Lys  Phe Phe Glu Glu Leu  Ile Lys Leu 
    1115                 1120                 1125             


Phe Arg  Leu Thr Leu Gln Met  Arg Asn Ser Ile Ser  Gly Arg Thr 
    1130                 1135                 1140             


Asp Val  Asp Tyr Leu Ile Ser  Pro Val Lys Asn Ser  Asn Gly Tyr 
    1145                 1150                 1155             


Phe Tyr  Asn Ser Asn Asp Tyr  Lys Lys Glu Gly Ala  Lys Tyr Pro 
    1160                 1165                 1170             


Lys Asp  Ala Asp Ala Asn Gly  Ala Tyr Asn Ile Ala  Arg Lys Val 
    1175                 1180                 1185             


Leu Trp  Ala Ile Glu Gln Phe  Lys Met Ala Asp Glu  Asp Lys Leu 
    1190                 1195                 1200             


Asp Lys  Thr Lys Ile Ser Ile  Lys Asn Gln Glu Trp  Leu Glu Tyr 
    1205                 1210                 1215             


Ala Gln  Thr His Cys Glu 
    1220                 


<210>  41
<211>  529
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cas14a.1

<400>  41

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


Pro Tyr Asn Ser Ala Glu Val Glu Lys Ile Val Ala Asp Glu Lys Asn 
            20                  25                  30          


Asn Arg Glu Lys Ile Ala Leu Glu Lys Asn Lys Asp Lys Val Lys Glu 
        35                  40                  45              


Ala Cys Ser Lys His Leu Lys Val Ala Ala Tyr Cys Thr Thr Gln Val 
    50                  55                  60                  


Glu Arg Asn Ala Cys Leu Phe Cys Lys Ala Arg Lys Leu Asp Asp Lys 
65                  70                  75                  80  


Phe Tyr Gln Lys Leu Arg Gly Gln Phe Pro Asp Ala Val Phe Trp Gln 
                85                  90                  95      


Glu Ile Ser Glu Ile Phe Arg Gln Leu Gln Lys Gln Ala Ala Glu Ile 
            100                 105                 110         


Tyr Asn Gln Ser Leu Ile Glu Leu Tyr Tyr Glu Ile Phe Ile Lys Gly 
        115                 120                 125             


Lys Gly Ile Ala Asn Ala Ser Ser Val Glu His Tyr Leu Ser Asp Val 
    130                 135                 140                 


Cys Tyr Thr Arg Ala Ala Glu Leu Phe Lys Asn Ala Ala Ile Ala Ser 
145                 150                 155                 160 


Gly Leu Arg Ser Lys Ile Lys Ser Asn Phe Arg Leu Lys Glu Leu Lys 
                165                 170                 175     


Asn Met Lys Ser Gly Leu Pro Thr Thr Lys Ser Asp Asn Phe Pro Ile 
            180                 185                 190         


Pro Leu Val Lys Gln Lys Gly Gly Gln Tyr Thr Gly Phe Glu Ile Ser 
        195                 200                 205             


Asn His Asn Ser Asp Phe Ile Ile Lys Ile Pro Phe Gly Arg Trp Gln 
    210                 215                 220                 


Val Lys Lys Glu Ile Asp Lys Tyr Arg Pro Trp Glu Lys Phe Asp Phe 
225                 230                 235                 240 


Glu Gln Val Gln Lys Ser Pro Lys Pro Ile Ser Leu Leu Leu Ser Thr 
                245                 250                 255     


Gln Arg Arg Lys Arg Asn Lys Gly Trp Ser Lys Asp Glu Gly Thr Glu 
            260                 265                 270         


Ala Glu Ile Lys Lys Val Met Asn Gly Asp Tyr Gln Thr Ser Tyr Ile 
        275                 280                 285             


Glu Val Lys Arg Gly Ser Lys Ile Gly Glu Lys Ser Ala Trp Met Leu 
    290                 295                 300                 


Asn Leu Ser Ile Asp Val Pro Lys Ile Asp Lys Gly Val Asp Pro Ser 
305                 310                 315                 320 


Ile Ile Gly Gly Ile Asp Val Gly Val Lys Ser Pro Leu Val Cys Ala 
                325                 330                 335     


Ile Asn Asn Ala Phe Ser Arg Tyr Ser Ile Ser Asp Asn Asp Leu Phe 
            340                 345                 350         


His Phe Asn Lys Lys Met Phe Ala Arg Arg Arg Ile Leu Leu Lys Lys 
        355                 360                 365             


Asn Arg His Lys Arg Ala Gly His Gly Ala Lys Asn Lys Leu Lys Pro 
    370                 375                 380                 


Ile Thr Ile Leu Thr Glu Lys Ser Glu Arg Phe Arg Lys Lys Leu Ile 
385                 390                 395                 400 


Glu Arg Trp Ala Cys Glu Ile Ala Asp Phe Phe Ile Lys Asn Lys Val 
                405                 410                 415     


Gly Thr Val Gln Met Glu Asn Leu Glu Ser Met Lys Arg Lys Glu Asp 
            420                 425                 430         


Ser Tyr Phe Asn Ile Arg Leu Arg Gly Phe Trp Pro Tyr Ala Glu Met 
        435                 440                 445             


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


Lys Val Ala Pro Asn Asn Thr Ser Lys Thr Cys Ser Lys Cys Gly His 
465                 470                 475                 480 


Leu Asn Asn Tyr Phe Asn Phe Glu Tyr Arg Lys Lys Asn Lys Phe Pro 
                485                 490                 495     


His Phe Lys Cys Glu Lys Cys Asn Phe Lys Glu Asn Ala Asp Tyr Asn 
            500                 505                 510         


Ala Ala Leu Asn Ile Ser Asn Pro Lys Leu Lys Ser Thr Lys Glu Glu 
        515                 520                 525             


Pro 
    


<210>  42
<211>  7
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PAM


<220>
<221>  misc_feature
<222>  (1)..(5)
<223>  n is a, c, g, or t

<220>
<221>  misc_feature
<222>  (7)..(7)
<223>  n is a, c, g, or t

<400>  42
nnnnnyn                                                                  7


<210>  43
<211>  7
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PAM


<220>
<221>  misc_feature
<222>  (1)..(4)
<223>  n is a, c, g, or t

<220>
<221>  misc_feature
<222>  (7)..(7)
<223>  n is a, c, g, or t

<400>  43
nnnnyyn                                                                  7


<210>  44
<211>  7
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PAM


<220>
<221>  misc_feature
<222>  (1)..(4)
<223>  n is a, c, g, or t

<220>
<221>  misc_feature
<222>  (7)..(7)
<223>  n is a, c, g, or t

<400>  44
nnnnytn                                                                  7


<210>  45
<211>  7
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PAM


<220>
<221>  misc_feature
<222>  (1)..(4)
<223>  n is a, c, g, or t

<220>
<221>  misc_feature
<222>  (6)..(7)
<223>  n is a, c, g, or t

<400>  45
nnnnynn                                                                  7


<210>  46
<211>  8
<212>  DNA
<213>  Unknown

<220>
<223>  Kozak sequence

<400>  46
crccaugg                                                                 8


<210>  47
<211>  4
<212>  PRT
<213>  Unknown

<220>
<223>  N-terminal sequence

<400>  47

Met Glu Glu Lys 
1               


<210>  48
<211>  1159
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CasM26

<400>  48

Met Lys Val Thr Lys Val Gly Gly Ile Ser His Lys Lys Tyr Thr Ser 
1               5                   10                  15      


Glu Gly Arg Leu Val Lys Ser Glu Ser Glu Glu Asn Arg Thr Asp Glu 
            20                  25                  30          


Arg Leu Ser Ala Leu Leu Asn Met Arg Leu Asp Met Tyr Ile Lys Asn 
        35                  40                  45              


Pro Ser Ser Thr Glu Thr Lys Glu Asn Gln Lys Arg Ile Gly Lys Leu 
    50                  55                  60                  


Lys Lys Phe Phe Ser Asn Lys Met Val Tyr Leu Lys Asp Asn Thr Leu 
65                  70                  75                  80  


Ser Leu Lys Asn Gly Lys Lys Glu Asn Ile Asp Arg Glu Tyr Ser Glu 
                85                  90                  95      


Thr Asp Ile Leu Glu Ser Asp Val Arg Asp Lys Lys Asn Phe Ala Val 
            100                 105                 110         


Leu Lys Lys Ile Tyr Leu Asn Glu Asn Val Asn Ser Glu Glu Leu Glu 
        115                 120                 125             


Val Phe Arg Asn Asp Ile Lys Lys Lys Leu Asn Lys Ile Asn Ser Leu 
    130                 135                 140                 


Lys Tyr Ser Phe Glu Lys Asn Lys Ala Asn Tyr Gln Lys Ile Asn Glu 
145                 150                 155                 160 


Asn Asn Ile Glu Lys Val Glu Gly Lys Ser Lys Arg Asn Ile Ile Tyr 
                165                 170                 175     


Asp Tyr Tyr Arg Glu Ser Ala Lys Arg Asp Ala Tyr Val Ser Asn Val 
            180                 185                 190         


Lys Glu Ala Phe Asp Lys Leu Tyr Lys Glu Glu Asp Ile Ala Lys Leu 
        195                 200                 205             


Val Leu Glu Ile Glu Asn Leu Thr Lys Leu Glu Lys Tyr Lys Ile Arg 
    210                 215                 220                 


Glu Phe Tyr His Glu Ile Ile Gly Arg Lys Asn Asp Lys Glu Asn Phe 
225                 230                 235                 240 


Ala Lys Ile Ile Tyr Glu Glu Ile Gln Asn Val Asn Asn Met Lys Glu 
                245                 250                 255     


Leu Ile Glu Lys Val Pro Asp Met Ser Glu Leu Lys Lys Ser Gln Val 
            260                 265                 270         


Phe Tyr Lys Tyr Tyr Leu Asp Lys Glu Glu Leu Asn Asp Lys Asn Ile 
        275                 280                 285             


Lys Tyr Ala Phe Cys His Phe Val Glu Ile Glu Met Ser Gln Leu Leu 
    290                 295                 300                 


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


Lys Arg Ile Phe Glu Tyr Gln Asn Leu Lys Lys Leu Ile Glu Asn Lys 
                325                 330                 335     


Leu Leu Asn Lys Leu Asp Thr Tyr Val Arg Asn Cys Gly Lys Tyr Asn 
            340                 345                 350         


Tyr Tyr Leu Gln Asp Gly Glu Ile Ala Thr Ser Asp Phe Ile Ala Arg 
        355                 360                 365             


Asn Arg Gln Asn Glu Ala Phe Leu Arg Asn Ile Ile Gly Val Ser Ser 
    370                 375                 380                 


Val Ala Tyr Phe Ser Leu Arg Asn Ile Leu Glu Thr Glu Asn Glu Asn 
385                 390                 395                 400 


Asp Ile Thr Gly Arg Met Arg Gly Lys Thr Val Lys Asn Asn Lys Gly 
                405                 410                 415     


Glu Glu Lys Tyr Val Ser Gly Glu Val Asp Lys Ile Tyr Asn Glu Asn 
            420                 425                 430         


Lys Lys Asn Glu Val Lys Glu Asn Leu Lys Met Phe Tyr Ser Tyr Asp 
        435                 440                 445             


Phe Asn Met Asp Asn Lys Asn Glu Ile Glu Asp Phe Phe Ala Asn Ile 
    450                 455                 460                 


Asp Glu Ala Ile Ser Ser Ile Arg His Gly Ile Val His Phe Asn Leu 
465                 470                 475                 480 


Glu Leu Glu Gly Lys Asp Ile Phe Ala Phe Lys Asn Ile Ala Pro Ser 
                485                 490                 495     


Glu Ile Ser Lys Lys Met Phe Gln Asn Glu Ile Asn Glu Lys Lys Leu 
            500                 505                 510         


Lys Leu Lys Ile Phe Arg Gln Leu Asn Ser Ala Asn Val Phe Arg Tyr 
        515                 520                 525             


Leu Glu Lys Tyr Lys Ile Leu Asn Tyr Leu Lys Arg Thr Arg Phe Glu 
    530                 535                 540                 


Phe Val Asn Lys Asn Ile Pro Phe Val Pro Ser Phe Thr Lys Leu Tyr 
545                 550                 555                 560 


Ser Arg Ile Asp Asp Leu Lys Asn Ser Leu Gly Ile Tyr Trp Lys Thr 
                565                 570                 575     


Pro Lys Thr Asn Asp Asp Asn Lys Thr Lys Glu Ile Ile Asp Ala Gln 
            580                 585                 590         


Ile Tyr Leu Leu Lys Asn Ile Tyr Tyr Gly Glu Phe Leu Asn Tyr Phe 
        595                 600                 605             


Met Ser Asn Asn Gly Asn Phe Phe Glu Ile Ser Lys Glu Ile Ile Glu 
    610                 615                 620                 


Leu Asn Lys Asn Asp Lys Arg Asn Leu Lys Thr Gly Phe Tyr Lys Leu 
625                 630                 635                 640 


Gln Lys Phe Glu Asp Ile Gln Glu Lys Ile Pro Lys Glu Tyr Leu Ala 
                645                 650                 655     


Asn Ile Gln Ser Leu Tyr Met Ile Asn Ala Gly Asn Gln Asp Glu Glu 
            660                 665                 670         


Glu Lys Asp Thr Tyr Ile Asp Phe Ile Gln Lys Ile Phe Leu Lys Gly 
        675                 680                 685             


Phe Met Thr Tyr Leu Ala Asn Asn Gly Arg Leu Ser Leu Ile Tyr Ile 
    690                 695                 700                 


Gly Ser Asp Glu Glu Thr Asn Thr Ser Leu Ala Glu Lys Lys Gln Glu 
705                 710                 715                 720 


Phe Asp Lys Phe Leu Lys Lys Tyr Glu Gln Asn Asn Asn Ile Lys Ile 
                725                 730                 735     


Pro Tyr Glu Ile Asn Glu Phe Leu Arg Glu Ile Lys Leu Gly Asn Ile 
            740                 745                 750         


Leu Lys Tyr Thr Glu Arg Leu Asn Met Phe Tyr Leu Ile Leu Lys Leu 
        755                 760                 765             


Leu Asn His Lys Glu Leu Thr Asn Leu Lys Gly Ser Leu Glu Lys Tyr 
    770                 775                 780                 


Gln Ser Ala Asn Lys Glu Glu Ala Phe Ser Asp Gln Leu Glu Leu Ile 
785                 790                 795                 800 


Asn Leu Leu Asn Leu Asp Asn Asn Arg Val Thr Glu Asp Phe Glu Leu 
                805                 810                 815     


Glu Ala Asp Glu Ile Gly Lys Phe Leu Asp Phe Asn Gly Asn Lys Val 
            820                 825                 830         


Lys Asp Asn Lys Glu Leu Lys Lys Phe Asp Thr Asn Lys Ile Tyr Phe 
        835                 840                 845             


Asp Gly Glu Asn Ile Ile Lys His Arg Ala Phe Tyr Asn Ile Lys Lys 
    850                 855                 860                 


Tyr Gly Met Leu Asn Leu Leu Glu Lys Ile Ala Asp Lys Ala Gly Tyr 
865                 870                 875                 880 


Lys Ile Ser Ile Glu Glu Leu Lys Lys Tyr Ser Asn Lys Lys Asn Glu 
                885                 890                 895     


Ile Glu Lys Asn His Lys Met Gln Glu Asn Leu His Arg Lys Tyr Ala 
            900                 905                 910         


Arg Pro Arg Lys Asp Glu Lys Phe Thr Asp Glu Asp Tyr Glu Ser Tyr 
        915                 920                 925             


Lys Gln Ala Ile Glu Asn Ile Glu Glu Tyr Thr His Leu Lys Asn Lys 
    930                 935                 940                 


Val Glu Phe Asn Glu Leu Asn Leu Leu Gln Gly Leu Leu Leu Arg Ile 
945                 950                 955                 960 


Leu His Arg Leu Val Gly Tyr Thr Ser Ile Trp Glu Arg Asp Leu Arg 
                965                 970                 975     


Phe Arg Leu Lys Gly Glu Phe Pro Glu Asn Gln Tyr Ile Glu Glu Ile 
            980                 985                 990         


Phe Asn Phe Glu Asn Lys Lys Asn  Val Lys Tyr Lys Gly  Gly Gln Ile 
        995                 1000                 1005             


Val Glu  Lys Tyr Ile Lys Phe  Tyr Lys Glu Leu His  Gln Asn Asp 
    1010                 1015                 1020             


Glu Val  Lys Ile Asn Lys Tyr  Ser Ser Ala Asn Ile  Lys Val Leu 
    1025                 1030                 1035             


Lys Gln  Glu Lys Lys Asp Leu  Tyr Ile Arg Asn Tyr  Ile Ala His 
    1040                 1045                 1050             


Phe Asn  Tyr Ile Pro His Ala  Glu Ile Ser Leu Leu  Glu Val Leu 
    1055                 1060                 1065             


Glu Asn  Leu Arg Lys Leu Leu  Ser Tyr Asp Arg Lys  Leu Lys Asn 
    1070                 1075                 1080             


Ala Val  Met Lys Ser Val Val  Asp Ile Leu Lys Glu  Tyr Gly Phe 
    1085                 1090                 1095             


Val Ala  Thr Phe Lys Ile Gly  Ala Asp Lys Lys Ile  Gly Ile Gln 
    1100                 1105                 1110             


Thr Leu  Glu Ser Glu Lys Ile  Val His Leu Lys Asn  Leu Lys Lys 
    1115                 1120                 1125             


Lys Lys  Leu Met Thr Asp Arg  Asn Ser Glu Glu Leu  Cys Lys Leu 
    1130                 1135                 1140             


Val Lys  Ile Met Phe Glu Tyr  Lys Met Glu Glu Lys  Lys Ser Glu 
    1145                 1150                 1155             


Asn 
    


<210>  49
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  ss nucleic acid in a reporter

<400>  49
tttttttttt tttttttttt                                                   20


<210>  50
<211>  12
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  ss nucleic acid in a reporter

<400>  50
cccccccccc cc                                                           12


<210>  51
<211>  181
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  sgRNA

<400>  51
cuucacugau aaaguggaga accgcuucac caaaagcugu cccuuagggg auuagaacuu       60

gagugaaggu gggcugcuug caucagccua augucgagaa gugcuuucuu cggaaaguaa      120

cccucgaaac aaauucauuu gaaagaauga aggaaugcaa ccccccagcg cuucagcguu      180

c                                                                      181


<210>  52
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  crRNA

<400>  52
gaauuucuac uauuguagau gccgauaaug auguagggau                             40


<210>  53
<211>  41
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  crRNA

<400>  53
uaauuucuac uaaguguaga ugccgauaau gauguaggga u                           41


<210>  54
<211>  41
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  crRNA

<400>  54
uaauuucuac uaaguguaga ucccccagcg cuucagcguu c                           41


<210>  55
<211>  20
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  guide nucleic acid

<400>  55
gaauuucuac uauuguagau                                                   20


<210>  56
<211>  21
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  guide nucleic acid

<400>  56
uaauuucuac uaaguguaga u                                                 21


<210>  57
<211>  4
<212>  PRT
<213>  Unknown

<220>
<223>  N-terminal sequence

<400>  57

Met Leu Lys Ser 
1         

      