                         SEQUENCE LISTING

<110>  RAMOT AT TEL-AVIV UNIVERSITY LTD.
       OFFEN, Daniel
       ANGEL, Ariel
 
<120>  METHODS OF TREATING ALZHEIMER'S DISEASE

<130>  72941

<150>  US 62/478,715
<151>  2017-03-30

<160>  31    

<170>  PatentIn version 3.5

<210>  1
<211>  639
<212>  DNA
<213>  Mus musculus

<400>  1
gtgttcgatc cagccgagca gtacaagatg gaccacaaga ggagaggagt tgccctcatc       60

ttcaatcacg agaggttctt ttggcacctg accctcccag agaggcgggg caccaacgca      120

gacagagaca acctgactcg caggttttca gatctaggat ttgaagtgaa atgctttaac      180

gacctcagag cagaagaact cctgctcaaa attcacgagg tgtcgacttc aagccacata      240

gatgccgatt gcttcatctg tgtcttcctg agccatgggg aaggcaacca cgtttacgca      300

tacgacgcca aaattgaaat tcagacgttg actggcttgt tcaaaggaga caagtgtcag      360

agcctggttg gaaaacccaa gatatttatc atccaggcct gtcggggtag ccagcatgac      420

gtacccgtgg ttcccctgga catggtggat caccagacag acaagctgga caacgtgacc      480

caggtggatg ctgcgtccgt gtacacgctg ccggcagggg cagacttcct catgtgctac      540

tctgtcgcag aagggtatta ctctcaccga gaaactgtga atggctcctg gtacattcag      600

gatttgtgtg agatgctggc gaggtacggc agttccctg                             639


<210>  2
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  gRNA sequence

<400>  2
tagccagcat gacgtacccg                                                   20


<210>  3
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  gRNA sequence

<400>  3
attgaaattc agacgttgac                                                   20


<210>  4
<211>  1661
<212>  DNA
<213>  homo sapiens

<400>  4
ccgagggcgg ggccgggccc gggagcctgt ggcttcagga agaggagggc aaggtgtctg       60

gctgcgcgtt tggctgcaat gagctcggcc tcggggctcc gcagggggca cccggcaggt      120

ggggaagaaa acatgacaga aacagatgcc ttctataaaa gagaaatgtt tgatccggca      180

gaaaagtaca aaatggacca caggaggaga ggaattgctt taatcttcaa tcatgagagg      240

ttcttttggc acttaacact gccagaaagg cggggcacct gcgcagatag agacaatctt      300

acccgcaggt tttcagatct aggatttgaa gtgaaatgct ttaatgatct taaagcagaa      360

gaactactgc tcaaaattca tgaggtgtca actgttagcc acgcagatgc cgattgcttt      420

gtgtgtgtct tcctgagcca tggcgaaggc aatcacattt atgcatatga tgctaaaatc      480

gaaattcaga cattaactgg cttgttcaaa ggagacaagt gtcacagcct ggttggaaaa      540

cccaagatat ttatcattca ggcatgtcgg ggaaaccagc acgatgtgcc agtcattcct      600

ttggatgtag tagataatca gacagagaag ttggacacca acataactga ggtggatgca      660

gcctccgttt acacgctgcc tgctggagct gacttcctca tgtgttactc tgttgcagaa      720

ggatattatt ctcaccggga aactgtgaac ggctcatggt acattcaaga tttgtgtgag      780

atgttgggaa aatatggctc ctccttagag ttcacagaac tcctcacact ggtgaacagg      840

aaagtttctc agcgccgagt ggacttttgc aaagacccaa gtgcaattgg aaagaagcag      900

gttccctgtt ttgcctcaat gctaactaaa aagctgcatt tctttccaaa atctaattaa      960

ttaatagagg ctatctaatt ttacactctg tattgaaaat ggctttctca gccaggcgtg     1020

gttactcaca cctgtaatcc cagcactttg ggagtccaag gtgggcggat cacctgaggt     1080

cgggagttcg agaccagcct gaccaacatg gagaagcccc gtctctacta aaaatgcaaa     1140

aaaaaattta gctaggcatg gcggcgcatg cctgcaatcc cagctacttg gaaggctgag     1200

gcaggagaat cacttgaacc caggaggtgg aggctgcggt gagccgagat tgcgccattg     1260

cactccagcc tgggcaacga gtgaaactcc gtctcaaaaa aaagaaaatg tctttctctt     1320

ccttttatat aaatatcgtt agggtgaagc attatggtct aatgattcaa atgttttaaa     1380

gtttaatgcc tagcagagaa ctgccttaaa aaaaaaaaaa aaaagttcat gttggccatg     1440

gtgaaagggt ttgatatgga gaaacaaaat cctcaggaaa ttagataaat aaaaatttat     1500

aagcatttgt attatttttt aataaactgc agggttacac aaaaatctag ctgatttaac     1560

ttgtattttg tcactttttt ataaaagttt attgtttgat gtttttaaag gtttttgaaa     1620

tccaggaatt aaatcatccc ttaataaaat attcgaaatt c                         1661


<210>  5
<211>  1394
<212>  DNA
<213>  homo sapiens

<400>  5
ccgagggcgg ggccgggccc gggagcctgt ggcttcagga agaggagggc aaggtgtctg       60

gctgcgcgtt tggctgcaat gagctcggcc tcggggctcc gcagggggca cccggcagtg      120

tcaactgtta gccacgcaga tgccgattgc tttgtgtgtg tcttcctgag ccatggcgaa      180

ggcaatcaca tttatgcata tgatgctaaa atcgaaattc agacattaac tggcttgttc      240

aaaggagaca agtgtcacag cctggttgga aaacccaaga tatttatcat tcaggcatgt      300

cggggaaacc agcacgatgt gccagtcatt cctttggatg tagtagataa tcagacagag      360

aagttggaca ccaacataac tgaggtggat gcagcctccg tttacacgct gcctgctgga      420

gctgacttcc tcatgtgtta ctctgttgca gaaggatatt attctcaccg ggaaactgtg      480

aacggctcat ggtacattca agatttgtgt gagatgttgg gaaaatatgg ctcctcctta      540

gagttcacag aactcctcac actggtgaac aggaaagttt ctcagcgccg agtggacttt      600

tgcaaagacc caagtgcaat tggaaagaag caggttccct gttttgcctc aatgctaact      660

aaaaagctgc atttctttcc aaaatctaat taattaatag aggctatcta attttacact      720

ctgtattgaa aatggctttc tcagccaggc gtggttactc acacctgtaa tcccagcact      780

ttgggagtcc aaggtgggcg gatcacctga ggtcgggagt tcgagaccag cctgaccaac      840

atggagaagc cccgtctcta ctaaaaatgc aaaaaaaaat ttagctaggc atggcggcgc      900

atgcctgcaa tcccagctac ttggaaggct gaggcaggag aatcacttga acccaggagg      960

tggaggctgc ggtgagccga gattgcgcca ttgcactcca gcctgggcaa cgagtgaaac     1020

tccgtctcaa aaaaaagaaa atgtctttct cttcctttta tataaatatc gttagggtga     1080

agcattatgg tctaatgatt caaatgtttt aaagtttaat gcctagcaga gaactgcctt     1140

aaaaaaaaaa aaaaaaagtt catgttggcc atggtgaaag ggtttgatat ggagaaacaa     1200

aatcctcagg aaattagata aataaaaatt tataagcatt tgtattattt tttaataaac     1260

tgcagggtta cacaaaaatc tagctgattt aacttgtatt ttgtcacttt tttataaaag     1320

tttattgttt gatgttttta aaggtttttg aaatccagga attaaatcat cccttaataa     1380

aatattcgaa attc                                                       1394


<210>  6
<211>  5
<212>  PRT
<213>  Artificial sequence

<220>
<223>  protospacer adjacent motif amino acid sequence

<400>  6

Asn Asn Gly Arg Arg 
1               5   


<210>  7
<211>  8
<212>  PRT
<213>  Artificial sequence

<220>
<223>  protospacer adjacent motif amino acid sequence

<400>  7

Asn Asn Asn Asn Gly Ala Thr Thr 
1               5               


<210>  8
<211>  8
<212>  PRT
<213>  Artificial sequence

<220>
<223>  protospacer adjacent motif amino acid sequence

<400>  8

Asn Asn Asn Asn Gly Asn Asn Asn 
1               5               


<210>  9
<211>  1381
<212>  PRT
<213>  Artificial sequence

<220>
<223>  AMINO ACID SEQUENCE OF THE Humanized CAS9

<400>  9

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


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


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


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


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


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


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


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


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


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


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


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


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


Asp Ala Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu 
    210                 215                 220                 


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


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


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


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


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


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


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


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


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


Ala Ser Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys 
    370                 375                 380                 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Glu Phe  Val Tyr Gly Asp Tyr  Lys Val Tyr Asp Val  Arg Lys Met 
    1010                 1015                 1020             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Gly Asp  Ser Arg Ala Asp Pro  Lys Lys Lys Arg Lys  Val 
    1370                 1375                 1380     


<210>  10
<211>  4146
<212>  DNA
<213>  Artificial sequence

<220>
<223>  NUCLEIC ACID SEQUENCE OF THE  Humanized CAS9

<400>  10
gccaccatgg acaagaagta ctccattggg ctcgatatcg gcacaaacag cgtcggctgg       60

gccgtcatta cggacgagta caaggtgccg agcaaaaaat tcaaagttct gggcaatacc      120

gatcgccaca gcataaagaa gaacctcatt ggcgccctcc tgttcgactc cggggagacg      180

gccgaagcca cgcggctcaa aagaacagca cggcgcagat atacccgcag aaagaatcgg      240

atctgctacc tgcaggagat ctttagtaat gagatggcta aggtggatga ctctttcttc      300

cataggctgg aggagtcctt tttggtggag gaggataaaa agcacgagcg ccacccaatc      360

tttggcaata tcgtggacga ggtggcgtac catgaaaagt acccaaccat atatcatctg      420

aggaagaagc ttgtagacag tactgataag gctgacttgc ggttgatcta tctcgcgctg      480

gcgcatatga tcaaatttcg gggacacttc ctcatcgagg gggacctgaa cccagacaac      540

agcgatgtcg acaaactctt tatccaactg gttcagactt acaatcagct tttcgaagag      600

aacccgatca acgcatccgg agttgacgcc aaagcaatcc tgagcgctag gctgtccaaa      660

tcccggcggc tcgaaaacct catcgcacag ctccctgggg agaagaagaa cggcctgttt      720

ggtaatctta tcgccctgtc actcgggctg acccccaact ttaaatctaa cttcgacctg      780

gccgaagatg ccaagcttca actgagcaaa gacacctacg atgatgatct cgacaatctg      840

ctggcccaga tcggcgacca gtacgcagac ctttttttgg cggcaaagaa cctgtcagac      900

gccattctgc tgagtgatat tctgcgagtg aacacggaga tcaccaaagc tccgctgagc      960

gctagtatga tcaagcgcta tgatgagcac caccaagact tgactttgct gaaggccctt     1020

gtcagacagc aactgcctga gaagtacaag gaaattttct tcgatcagtc taaaaatggc     1080

tacgccggat acattgacgg cggagcaagc caggaggaat tttacaaatt tattaagccc     1140

atcttggaaa aaatggacgg caccgaggag ctgctggtaa agcttaacag agaagatctg     1200

ttgcgcaaac agcgcacttt cgacaatgga agcatccccc accagattca cctgggcgaa     1260

ctgcacgcta tcctcaggcg gcaagaggat ttctacccct ttttgaaaga taacagggaa     1320

aagattgaga aaatcctcac atttcggata ccctactatg taggccccct cgcccgggga     1380

aattccagat tcgcgtggat gactcgcaaa tcagaagaga ccatcactcc ctggaacttc     1440

gaggaagtcg tggataaggg ggcctctgcc cagtccttca tcgaaaggat gactaacttt     1500

gataaaaatc tgcctaacga aaaggtgctt cctaaacact ctctgctgta cgagtacttc     1560

acagtttata acgagctcac caaggtcaaa tacgtcacag aagggatgag aaagccagca     1620

ttcctgtctg gagagcagaa gaaagctatc gtggacctcc tcttcaagac gaaccggaaa     1680

gttaccgtga aacagctcaa agaagactat ttcaaaaaga ttgaatgttt cgactctgtt     1740

gaaatcagcg gagtggagga tcgcttcaac gcatccctgg gaacgtatca cgatctcctg     1800

aaaatcatta aagacaagga cttcctggac aatgaggaga acgaggacat tcttgaggac     1860

attgtcctca cccttacgtt gtttgaagat agggagatga ttgaagaacg cttgaaaact     1920

tacgctcatc tcttcgacga caaagtcatg aaacagctca agaggcgccg atatacagga     1980

tgggggcggc tgtcaagaaa actgatcaat gggatccgag acaagcagag tggaaagaca     2040

atcctggatt ttcttaagtc cgatggattt gccaaccgga acttcatgca gttgatccat     2100

gatgactctc tcacctttaa ggaggacatc cagaaagcac aagtttctgg ccagggggac     2160

agtcttcacg agcacatcgc taatcttgca ggtagcccag ctatcaaaaa gggaatactg     2220

cagaccgtta aggtcgtgga tgaactcgtc aaagtaatgg gaaggcataa gcccgagaat     2280

atcgttatcg agatggcccg agagaaccaa actacccaga agggacagaa gaacagtagg     2340

gaaaggatga agaggattga agagggtata aaagaactgg ggtcccaaat ccttaaggaa     2400

cacccagttg aaaacaccca gcttcagaat gagaagctct acctgtacta cctgcagaac     2460

ggcagggaca tgtacgtgga tcaggaactg gacatcaatc ggctctccga ctacgacgtg     2520

gatcatatcg tgccccagtc ttttctcaaa gatgattcta ttgataataa agtgttgaca     2580

agatccgata aaaatagagg gaagagtgat aacgtcccct cagaagaagt tgtcaagaaa     2640

atgaaaaatt attggcggca gctgctgaac gccaaactga tcacacaacg gaagttcgat     2700

aatctgacta aggctgaacg aggtggcctg tctgagttgg ataaagccgg cttcatcaaa     2760

aggcagcttg ttgagacacg ccagatcacc aagcacgtgg cccaaattct cgattcacgc     2820

atgaacacca agtacgatga aaatgacaaa ctgattcgag aggtgaaagt tattactctg     2880

aagtctaagc tggtctcaga tttcagaaag gactttcagt tttataaggt gagagagatc     2940

aacaattacc accatgcgca tgatgcctac ctgaatgcag tggtaggcac tgcacttatc     3000

aaaaaatatc ccaagcttga atctgaattt gtttacggag actataaagt gtacgatgtt     3060

aggaaaatga tcgcaaagtc tgagcaggaa ataggcaagg ccaccgctaa gtacttcttt     3120

tacagcaata ttatgaattt tttcaagacc gagattacac tggccaatgg agagattcgg     3180

aagcgaccac ttatcgaaac aaacggagaa acaggagaaa tcgtgtggga caagggtagg     3240

gatttcgcga cagtccggaa ggtcctgtcc atgccgcagg tgaacatcgt taaaaagacc     3300

gaagtacaga ccggaggctt ctccaaggaa agtatcctcc cgaaaaggaa cagcgacaag     3360

ctgatcgcac gcaaaaaaga ttgggacccc aagaaatacg gcggattcga ttctcctaca     3420

gtcgcttaca gtgtactggt tgtggccaaa gtggagaaag ggaagtctaa aaaactcaaa     3480

agcgtcaagg aactgctggg catcacaatc atggagcgat caagcttcga aaaaaacccc     3540

atcgactttc tcgaggcgaa aggatataaa gaggtcaaaa aagacctcat cattaagctt     3600

cccaagtact ctctctttga gcttgaaaac ggccggaaac gaatgctcgc tagtgcgggc     3660

gagctgcaga aaggtaacga gctggcactg ccctctaaat acgttaattt cttgtatctg     3720

gccagccact atgaaaagct caaagggtct cccgaagata atgagcagaa gcagctgttc     3780

gtggaacaac acaaacacta ccttgatgag atcatcgagc aaataagcga attctccaaa     3840

agagtgatcc tcgccgacgc taacctcgat aaggtgcttt ctgcttacaa taagcacagg     3900

gataagccca tcagggagca ggcagaaaac attatccact tgtttactct gaccaacttg     3960

ggcgcgcctg cagccttcaa gtacttcgac accaccatag acagaaagcg gtacacctct     4020

acaaaggagg tcctggacgc cacactgatt catcagtcaa ttacggggct ctatgaaaca     4080

agaatcgacc tctctcagct cggtggagac agcagggctg accccaagaa gaagaggaag     4140

gtgtga                                                                4146


<210>  11
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Protein transduction domains

<400>  11

Pro Lys Lys Lys Arg Lys Val 
1               5           


<210>  12
<211>  11
<212>  PRT
<213>  Artificial sequence

<220>
<223>  nuclear localization signal amino acid sequence

<400>  12

Ser Pro Lys Lys Lys Arg Lys Val Glu Ala Ser 
1               5                   10      


<210>  13
<211>  6
<212>  PRT
<213>  Artificial sequence

<220>
<223>  nuclear localization signal amino acid sequence

<400>  13

Lys Lys Lys Arg Lys Val 
1               5       


<210>  14
<211>  18
<212>  PRT
<213>  Artificial sequence

<220>
<223>  nuclear localization signal amino acid sequence

<400>  14

Ser Pro Lys Lys Lys Arg Lys Val Glu Ala Ser Pro Lys Lys Lys Arg 
1               5                   10                  15      


Lys Val 
        


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

<220>
<223>  nuclear localization signal amino acid sequence

<400>  15

Lys Lys Lys Arg Lys 
1               5   


<210>  16
<211>  11
<212>  PRT
<213>  Artificial sequence

<220>
<223>  nuclear localization signal amino acid sequence

<400>  16

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg 
1               5                   10      


<210>  17
<211>  12
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Protein transduction domains

<400>  17

Arg Arg Gln Arg Arg Thr Ser Lys Leu Met Lys Arg 
1               5                   10          


<210>  18
<211>  27
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Protein transduction domains

<400>  18

Gly Trp Thr Leu Asn Ser Ala Gly Tyr Leu Leu Gly Lys Ile Asn Leu 
1               5                   10                  15      


Lys Ala Leu Ala Ala Leu Ala Lys Lys Ile Leu 
            20                  25          


<210>  19
<211>  33
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Protein transduction domains

<400>  19

Lys Ala Leu Ala Trp Glu Ala Lys Leu Ala Lys Ala Leu Ala Lys Ala 
1               5                   10                  15      


Leu Ala Lys His Leu Ala Lys Ala Leu Ala Lys Ala Leu Lys Cys Glu 
            20                  25                  30          


Ala 
    


<210>  20
<211>  16
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Protein transduction domains

<400>  20

Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys 
1               5                   10                  15      


<210>  21
<211>  8
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Protein transduction domains

<400>  21

Lys Lys Arg Arg Gln Arg Arg Arg 
1               5               


<210>  22
<211>  9
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Protein transduction domains

<400>  22

Arg Lys Lys Arg Arg Gln Arg Arg Arg 
1               5                   


<210>  23
<211>  14
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Protein transduction domains

<400>  23

Ser Gly Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Cys 
1               5                   10                  


<210>  24
<211>  11
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Protein transduction domains

<400>  24

Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg 
1               5                   10      


<210>  25
<211>  8
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Protein transduction domains

<400>  25

Lys Lys Arg Arg Gln Arg Arg Arg 
1               5               


<210>  26
<211>  21
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Protein transduction domains

<400>  26

Lys Glu Thr Trp Trp Glu Thr Trp Trp Thr Glu Trp Ser Gln Pro Lys 
1               5                   10                  15      


Lys Lys Arg Lys Val 
            20      


<210>  27
<211>  9
<212>  RNA
<213>  Artificial sequence

<220>
<223>  Examples of oligonucleotide sequences that can be used to form 
       the loop

<400>  27
uucaagaga                                                                9


<210>  28
<211>  9
<212>  RNA
<213>  Artificial sequence

<220>
<223>  Examples of oligonucleotide sequences that can be used to form 
       the loop

<400>  28
uuuguguag                                                                9


<210>  29
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  gRNA sequence

<400>  29
atagagacaa tcttacccgc                                                   20


<210>  30
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  gRNA sequence

<400>  30
aagattgtct ctatctgcgc                                                   20


<210>  31
<211>  20
<212>  DNA
<213>  Artificial sequence

<220>
<223>  gRNA sequence

<400>  31
gaatgactgg cacatcgtgc                                                   20


