                         SEQUENCE LISTING

<110>  Christiana Care Health Services, Inc.
       Kmiec, Eric
       Bialk, Pawel
       Yoo, Byung Chung
       Rivera-Torres, Natalia
 
<120>  AAV delivery system for lung cancer treatment 

<130>  130949-00620

<150>  US 63/029,212
<151>  2020-05-22

<150>  US 63/012,737
<151>  2020-04-20

<160>  128    

<170>  PatentIn version 3.5

<210>  1
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition element

<400>  1
agctactctg gcccttatag tcc                                               23


<210>  2
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  2
ucgaugugac cgggaauauc agg                                               23


<210>  3
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition element

<400>  3
actaaatctg ccatacgttg tcc                                               23


<210>  4
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  4
ugauuuagac gguaugcaac agg                                               23


<210>  5
<211>  28
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer

<400>  5
gtagtggtgc cttagagctt actcatcc                                          28


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

<220>
<223>  Primer

<400>  6
ctagcatggg cagtactcat gactaag                                           27


<210>  7
<211>  2446
<212>  DNA
<213>  Homo sapiens

<400>  7
gattaccgag tgccggggag cccggaggag ccgccgacgc agccgccacc gccgccgccg       60

ccgccaccag agccgccctg tccgcgccgc gcctcggcag ccggaacagg gccgccgtcg      120

gggagcccca acacacggtc cacagctcat catgatggac ttggagctgc cgccgccggg      180

actcccgtcc cagcaggaca tggatttgat tgacatactt tggaggcaag atatagatct      240

tggagtaagt cgagaagtat ttgacttcag tcagcgacgg aaagagtatg agctggaaaa      300

acagaaaaaa cttgaaaagg aaagacaaga acaactccaa aaggagcaag agaaagcctt      360

tttcgctcag ttacaactag atgaagagac aggtgaattt ctcccaattc agccagccca      420

gcacatccag tcagaaacca gtggatctgc caactactcc caggttgccc acattcccaa      480

atcagatgct ttgtactttg atgactgcat gcagcttttg gcgcagacat tcccgtttgt      540

agatgacaat gaggtttctt cggctacgtt tcagtcactt gttcctgata ttcccggtca      600

catcgagagc ccagtcttca ttgctactaa tcaggctcag tcacctgaaa cttctgttgc      660

tcaggtagcc cctgttgatt tagacggtat gcaacaggac attgagcaag tttgggagga      720

gctattatcc attcctgagt tacagtgtct taatattgaa aatgacaagc tggttgagac      780

taccatggtt ccaagtccag aagccaaact gacagaagtt gacaattatc atttttactc      840

atctataccc tcaatggaaa aagaagtagg taactgtagt ccacattttc ttaatgcttt      900

tgaggattcc ttcagcagca tcctctccac agaagacccc aaccagttga cagtgaactc      960

attaaattca gatgccacag tcaacacaga ttttggtgat gaattttatt ctgctttcat     1020

agctgagccc agtatcagca acagcatgcc ctcacctgct actttaagcc attcactctc     1080

tgaacttcta aatgggccca ttgatgtttc tgatctatca ctttgcaaag ctttcaacca     1140

aaaccaccct gaaagcacag cagaattcaa tgattctgac tccggcattt cactaaacac     1200

aagtcccagt gtggcatcac cagaacactc agtggaatct tccagctatg gagacacact     1260

acttggcctc agtgattctg aagtggaaga gctagatagt gcccctggaa gtgtcaaaca     1320

gaatggtcct aaaacaccag tacattcttc tggggatatg gtacaaccct tgtcaccatc     1380

tcaggggcag agcactcacg tgcatgatgc ccaatgtgag aacacaccag agaaagaatt     1440

gcctgtaagt cctggtcatc ggaaaacccc attcacaaaa gacaaacatt caagccgctt     1500

ggaggctcat ctcacaagag atgaacttag ggcaaaagct ctccatatcc cattccctgt     1560

agaaaaaatc attaacctcc ctgttgttga cttcaacgaa atgatgtcca aagagcagtt     1620

caatgaagct caacttgcat taattcggga tatacgtagg aggggtaaga ataaagtggc     1680

tgctcagaat tgcagaaaaa gaaaactgga aaatatagta gaactagagc aagatttaga     1740

tcatttgaaa gatgaaaaag aaaaattgct caaagaaaaa ggagaaaatg acaaaagcct     1800

tcacctactg aaaaaacaac tcagcacctt atatctcgaa gttttcagca tgctacgtga     1860

tgaagatgga aaaccttatt ctcctagtga atactccctg cagcaaacaa gagatggcaa     1920

tgttttcctt gttcccaaaa gtaagaagcc agatgttaag aaaaactaga tttaggagga     1980

tttgaccttt tctgagctag tttttttgta ctattatact aaaagctcct actgtgatgt     2040

gaaatgctca tactttataa gtaattctat gcaaaatcat agccaaaact agtatagaaa     2100

ataatacgaa actttaaaaa gcattggagt gtcagtatgt tgaatcagta gtttcacttt     2160

aactgtaaac aatttcttag gacaccattt gggctagttt ctgtgtaagt gtaaatacta     2220

caaaaactta tttatactgt tcttatgtca tttgttatat tcatagattt atatgatgat     2280

atgacatctg gctaaaaaga aattattgca aaactaacca ctatgtactt ttttataaat     2340

actgtatgga caaaaaatgg cattttttat attaaattgt ttagctctgg caaaaaaaaa     2400

aaattttaag agctggtact aataaaggat tattatgact gttaaa                    2446


<210>  8
<211>  605
<212>  PRT
<213>  Homo sapiens

<400>  8

Met Met Asp Leu Glu Leu Pro Pro Pro Gly Leu Pro Ser Gln Gln Asp 
1               5                   10                  15      


Met Asp Leu Ile Asp Ile Leu Trp Arg Gln Asp Ile Asp Leu Gly Val 
            20                  25                  30          


Ser Arg Glu Val Phe Asp Phe Ser Gln Arg Arg Lys Glu Tyr Glu Leu 
        35                  40                  45              


Glu Lys Gln Lys Lys Leu Glu Lys Glu Arg Gln Glu Gln Leu Gln Lys 
    50                  55                  60                  


Glu Gln Glu Lys Ala Phe Phe Ala Gln Leu Gln Leu Asp Glu Glu Thr 
65                  70                  75                  80  


Gly Glu Phe Leu Pro Ile Gln Pro Ala Gln His Ile Gln Ser Glu Thr 
                85                  90                  95      


Ser Gly Ser Ala Asn Tyr Ser Gln Val Ala His Ile Pro Lys Ser Asp 
            100                 105                 110         


Ala Leu Tyr Phe Asp Asp Cys Met Gln Leu Leu Ala Gln Thr Phe Pro 
        115                 120                 125             


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


Pro Asp Ile Pro Gly His Ile Glu Ser Pro Val Phe Ile Ala Thr Asn 
145                 150                 155                 160 


Gln Ala Gln Ser Pro Glu Thr Ser Val Ala Gln Val Ala Pro Val Asp 
                165                 170                 175     


Leu Asp Gly Met Gln Gln Asp Ile Glu Gln Val Trp Glu Glu Leu Leu 
            180                 185                 190         


Ser Ile Pro Glu Leu Gln Cys Leu Asn Ile Glu Asn Asp Lys Leu Val 
        195                 200                 205             


Glu Thr Thr Met Val Pro Ser Pro Glu Ala Lys Leu Thr Glu Val Asp 
    210                 215                 220                 


Asn Tyr His Phe Tyr Ser Ser Ile Pro Ser Met Glu Lys Glu Val Gly 
225                 230                 235                 240 


Asn Cys Ser Pro His Phe Leu Asn Ala Phe Glu Asp Ser Phe Ser Ser 
                245                 250                 255     


Ile Leu Ser Thr Glu Asp Pro Asn Gln Leu Thr Val Asn Ser Leu Asn 
            260                 265                 270         


Ser Asp Ala Thr Val Asn Thr Asp Phe Gly Asp Glu Phe Tyr Ser Ala 
        275                 280                 285             


Phe Ile Ala Glu Pro Ser Ile Ser Asn Ser Met Pro Ser Pro Ala Thr 
    290                 295                 300                 


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


Asp Leu Ser Leu Cys Lys Ala Phe Asn Gln Asn His Pro Glu Ser Thr 
                325                 330                 335     


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


Ser Val Ala Ser Pro Glu His Ser Val Glu Ser Ser Ser Tyr Gly Asp 
        355                 360                 365             


Thr Leu Leu Gly Leu Ser Asp Ser Glu Val Glu Glu Leu Asp Ser Ala 
    370                 375                 380                 


Pro Gly Ser Val Lys Gln Asn Gly Pro Lys Thr Pro Val His Ser Ser 
385                 390                 395                 400 


Gly Asp Met Val Gln Pro Leu Ser Pro Ser Gln Gly Gln Ser Thr His 
                405                 410                 415     


Val His Asp Ala Gln Cys Glu Asn Thr Pro Glu Lys Glu Leu Pro Val 
            420                 425                 430         


Ser Pro Gly His Arg Lys Thr Pro Phe Thr Lys Asp Lys His Ser Ser 
        435                 440                 445             


Arg Leu Glu Ala His Leu Thr Arg Asp Glu Leu Arg Ala Lys Ala Leu 
    450                 455                 460                 


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


Phe Asn Glu Met Met Ser Lys Glu Gln Phe Asn Glu Ala Gln Leu Ala 
                485                 490                 495     


Leu Ile Arg Asp Ile Arg Arg Arg Gly Lys Asn Lys Val Ala Ala Gln 
            500                 505                 510         


Asn Cys Arg Lys Arg Lys Leu Glu Asn Ile Val Glu Leu Glu Gln Asp 
        515                 520                 525             


Leu Asp His Leu Lys Asp Glu Lys Glu Lys Leu Leu Lys Glu Lys Gly 
    530                 535                 540                 


Glu Asn Asp Lys Ser Leu His Leu Leu Lys Lys Gln Leu Ser Thr Leu 
545                 550                 555                 560 


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


Ser Pro Ser Glu Tyr Ser Leu Gln Gln Thr Arg Asp Gly Asn Val Phe 
            580                 585                 590         


Leu Val Pro Lys Ser Lys Lys Pro Asp Val Lys Lys Asn 
        595                 600                 605 


<210>  9
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  9
tcgatgtgac cgggaatatc agg                                               23


<210>  10
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  10
tgatttagac ggtatgcaac agg                                               23


<210>  11
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  11
aagtacaaag catctgattt ggg                                               23


<210>  12
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  12
agcatctgat ttgggaatgt ggg                                               23


<210>  13
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  13
tggatttgat tgacatactt tgg                                               23


<210>  14
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  14
gcttcttact tttgggaaca agg                                               23


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

<220>
<223>  Guide RNA

<400>  15
tttgattgac atactttgga ggcaa                                             25


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

<220>
<223>  Guide RNA

<400>  16
ttttccttgt tcccaaaagt aagaa                                             25


<210>  17
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition sequence

<400>  17
aaactaactg tatgaaacct ccc                                               23


<210>  18
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  18
uuugauugac auacuuugga ggg                                               23


<210>  19
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition element

<400>  19
gaatgaggtt ctagatatag acc                                               23


<210>  20
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  20
cuuacuccaa gaucuauauc ugg                                               23


<210>  21
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition sequence

<400>  21
tatgaaacct ccgttctata tcc                                               23


<210>  22
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  22
auacuuugga ggcaagauau agg                                               23


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

<220>
<223>  Guide RNA recognition element

<400>  23
tccgttctat atctagaacc tcc                                               23


<210>  24
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  24
aggcaagaua uagaucuugg agg                                               23


<210>  25
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition element

<400>  25
ctatatctag aacctcattc acc                                               23


<210>  26
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  26
gauauagauc uuggaguaag ugg                                               23


<210>  27
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition element

<400>  27
actgacttca gtttatgaag acc                                               23


<210>  28
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  28
ugacugaagu caaauacuuc ugg                                               23


<210>  29
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition element

<400>  29
aagtagatca acattgactc gcc                                               23


<210>  30
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  30
uucaucuagu uguaacugag cgg                                               23


<210>  31
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition element

<400>  31
taagtggaca gagaagtaga tcc                                               23


<210>  32
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  32
auucaccugu cucuucaucu agg                                               23


<210>  33
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition element

<400>  33
gagtcaatgt tgatctactt ccc                                               23


<210>  34
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  34
cucaguuaca acuagaugaa ggg                                               23


<210>  35
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition element

<400>  35
acttaaccct ctttaagtgg acc                                               23


<210>  36
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  36
ugaauuggga gaaauucacc ugg                                               23


<210>  37
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition element

<400>  37
gttgatctac ttctctgtcc acc                                               23


<210>  38
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  38
caacuagaug aagagacagg ugg                                               23


<210>  39
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition element

<400>  39
tattatcgag gagggtttga acc                                               23


<210>  40
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  40
auaauagcuc cucccaaacu ugg                                               23


<210>  41
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  41
tttgattgac atactttgga ggg                                               23


<210>  42
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  42
cttactccaa gatctatatc tgg                                               23


<210>  43
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  43
atactttgga ggcaagatat agg                                               23


<210>  44
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  44
aggcaagata tagatcttgg agg                                               23


<210>  45
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  45
gatatagatc ttggagtaag tgg                                               23


<210>  46
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  46
tgactgaagt caaatacttc tgg                                               23


<210>  47
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  47
ttcatctagt tgtaactgag cgg                                               23


<210>  48
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  48
attcacctgt ctcttcatct agg                                               23


<210>  49
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  49
ctcagttaca actagatgaa ggg                                               23


<210>  50
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  50
tgaattggga gaaattcacc tgg                                               23


<210>  51
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  51
caactagatg aagagacagg tgg                                               23


<210>  52
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  52
ataatagctc ctcccaaact tgg                                               23


<210>  53
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition sequence

<400>  53
aaaaagcgag taatgttgat cc                                                22


<210>  54
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  54
uuuuucgcuc aguuacaacu agg                                               23


<210>  55
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA recognition sequence

<400>  55
gttgatctac ttctctgtcc acc                                               23


<210>  56
<211>  23
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  56
caacuagaug aagagacagg ugg                                               23


<210>  57
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  57
tttttcgctc agttacaact agg                                               23


<210>  58
<211>  23
<212>  DNA
<213>  Homo sapiens

<400>  58
caactagatg aagagacagg tgg                                               23


<210>  59
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  59
caagatatag atcttggagt aag                                               23


<210>  60
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  60
aagatataga tcttggagta ag                                                22


<210>  61
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  61
gatatagatc ttggagtaag                                                   20


<210>  62
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  62
tatagatctt ggagtaag                                                     18


<210>  63
<211>  17
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  63
atagatcttg gagtaag                                                      17


<210>  64
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  64
tggaggcaag atatagatct tgg                                               23


<210>  65
<211>  200
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  ssDNA template

<400>  65
ttaaaaaaca tgagctctct ccttcctttt tttgtcttaa acataggaca tggatttgat       60

tgacatactt tggaggcaag atatagatct tggagtaagt ggagaagtat ttgacttcag      120

tcagcgacgg aaagagtatg agctggaaaa acagaaaaaa cttgaaaagg aaagacaaga      180

acaactccaa aaggagcaag                                                  200


<210>  66
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  66
tcgatgtgac cgggaatatc agg                                               23


<210>  67
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Guide RNA

<400>  67
tgatttagac ggtatgcaac agg                                               23

<210>  68
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA1 recognition element

<400>  68
cctgatattc ccggtcacat cga                                               23


<210>  69
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA1 recognition element

<400>  69
ggactataag ggccagtgta gct                                               23


<210>  70
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  70
caccgtcgat gtgaccgcga atatc                                             25


<210>  71
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  71
cagctacact ggcccttata gcaaa                                             25


<210>  72
<211>  23
<212>  DNA
<213>  Artificial sequence

<220>
<223>  gRNA2 recognition element

<400>  72
tgatttagac ggtatgcaac agg                                               23


<210>  73
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA2 recognition element

<400>  73
actaaatctg ccatacgttg tcc                                               23


<210>  74
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  74
caccgtgatt tagacggtat gcaac                                             25


<210>  75
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  75
cactaaatct gccatacgtt gcaaa                                             25


<210>  76
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  76
tcgatgtgac cgggaatatc agg                                               23


<210>  77
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  77
tgatttagac ggtatgcaac agg                                               23


<210>  78
<211>  41
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA


<220>
<221>  misc_feature
<222>  (23)..(24)
<223>  n is a, c, g, or t

<220>
<221>  misc_feature
<222>  (27)..(27)
<223>  n is a, c, g, or t

<220>
<221>  misc_feature
<222>  (32)..(35)
<223>  n is a, c, g, or t

<220>
<221>  misc_feature
<222>  (41)..(41)
<223>  n is a, c, g, or t

<400>  78
tcagtcactt gttcctgata aannggnaat tnnnnaagtt n                           41


<210>  79
<211>  45
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  79
acgtttcagt cacttgttcc cgatcacatc gagagcccag tcttc                       45


<210>  80
<211>  172
<212>  DNA
<213>  Homo sapiens

<400>  80
ctctctcctt cctttttttg tctttttcat aggacatgga tttgattgac atactttgga       60

ggcaagtttt tgatcttgga gtaagtcgag aagtttttga cttcagtcag cgacggaaag      120

agtatgagct ggtttttcag aaaaaacttg aaaaggaaag acaagaacaa ct              172


<210>  81
<211>  171
<212>  DNA
<213>  Homo sapiens

<400>  81
agagaggaag caaaaaaaca gaaaaactat cctgtaccta aactaactgt atgaaacctc       60

ccttcaaaaa ctagaacctc attcagctct tcaaaaactg aagtcagtcg ctccctatct      120

catactcgac caaaaagtct aaaaagaact attccttact gttcttcttg a               171


<210>  82
<211>  26
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  82
caagatatag atcttggagt aagtgg                                            26


<210>  83
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  83
aagatataga tcttggagta agtgg                                             25


<210>  84
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  84
gatatagatc ttggagtaag tgg                                               23


<210>  85
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  85
tatagatctt ggagtaagtg g                                                 21


<210>  86
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  86
atagatcttg gagtaagtgg                                                   20


<210>  87
<211>  26
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  87
caagatatag atcttggagt aagtgg                                            26


<210>  88
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  88
aagatataga tcttggagta agtgg                                             25


<210>  89
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  89
gatatagatc ttggagtaag tgg                                               23


<210>  90
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  90
tatagatctt ggagtaagtg g                                                 21


<210>  91
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  91
atagatcttg gagtaagtgg                                                   20


<210>  92
<211>  120
<212>  DNA
<213>  Homo sapiens

<400>  92
tttttttgtc ttaaacatag gacatggatt tgattgacat actttggagg caagatatag       60

atcttggagt aagtcgagaa gtatttgact tcagtcagcg acggaaagag tatgagctgg      120


<210>  93
<211>  120
<212>  DNA
<213>  Homo sapiens

<400>  93
aaaaaaacag aatttgtatc ctgtacctaa actaactgta tgaaacctcc gttctatatc       60

tagaacctca ttcagctctt cataaactga agtcagtcgc tgcctttctc atactcgacc      120


<210>  94
<211>  120
<212>  DNA
<213>  Homo sapiens

<400>  94
aaaaacagaa aaaacttgaa aaggaaagac aagaacaact ccaaaaggag caagagaaag       60

cctttttcgc tcagttacaa ctagatgaag agacaggtga atttctccca attcagccag      120


<210>  95
<211>  120
<212>  DNA
<213>  Homo sapiens

<400>  95
tttttgtctt ttttgaactt ttcctttctg ttcttgttga ggttttcctc gttctctttc       60

ggaaaaagcg agtcaatgtt gatctacttc tctgtccact taaagagggt taagtcggtc      120


<210>  96
<211>  138
<212>  DNA
<213>  Homo sapiens

<400>  96
taggacatgg atttgattga catactttgg aggcaagata tagatcttgg agtaagaagt       60

atttgacttc agtcagcgac ggaaagagta tgagctggaa aaacagaaaa aacttgaaaa      120

ggaaagacaa gaacaact                                                    138


<210>  97
<211>  143
<212>  DNA
<213>  Homo sapiens

<400>  97
atcctgtacc taaactaact gtatgaaacc tccgttctat atctagaacc tcattcagct       60

cttcataaac tgaagtcagt cgctgccttt ctcatactcg acctttttgt cttttttgaa      120

cttttccttt ctgttcttgt tga                                              143


<210>  98
<211>  138
<212>  DNA
<213>  Homo sapiens

<400>  98
taggacatgg atttgattga catactttgg aggcaagata tagatcttgg agtaagaagt       60

atttgacttc agtcagcgac ggaaagagta tgagctggaa aaacagaaaa aacttgaaaa      120

ggaaagacaa gaacaact                                                    138


<210>  99
<211>  143
<212>  DNA
<213>  Homo sapiens

<400>  99
atcctgtacc taaactaact gtatgaaacc tccgttctat atctagaacc tcattcacct       60

cttcataaac tgaagtcagt cgctgccttt ctcatactcg acctttttgt cttttttgaa      120

cttttccttt ctgttcttgt tga                                              143


<210>  100
<211>  159
<212>  DNA
<213>  Homo sapiens

<400>  100
gacatggatt tgattgacat actttggagg caagatatag atcttggagt aagtcgagaa       60

gtatttgact tcagtcagcg acggaaagag tatgagctgg aaaaacagaa aaaacttgaa      120

aaggaaagac aagaacaact ccaaaaggag caagagaaa                             159


<210>  101
<211>  156
<212>  DNA
<213>  Homo sapiens

<400>  101
gacatggatt tgattgacat actttggagg caagatatag atcttggagt aaggagaagt       60

atttgacttc agtcaggacg gaaagagtat gagctggaaa aacagaaaaa acttgaaaag      120

gaaagacaag aacaactcca aaaggagcaa gagaaa                                156


<210>  102
<211>  159
<212>  DNA
<213>  Homo sapiens

<400>  102
gacatggatt tgattgacat actttggagg caagatatag atcttggagt aagtcgagaa       60

gtatttgact tcagtcagcg acggaaagag tatgagctgg aaaaacagaa aaaacttgaa      120

aaggaaagac aagaacaact ccaaaaggag caagagaaa                             159


<210>  103
<211>  81
<212>  DNA
<213>  Homo sapiens

<400>  103
ctttggagga agatatagat cttggagtaa gtcgagaagt atttgacttc agtagcgacg       60

gaaagagtat gagctggaaa a                                                 81


<210>  104
<211>  79
<212>  DNA
<213>  Homo sapiens

<400>  104
ctttggaggc aagatataga ggagtaagtg gagaagtatt tgacttcagt cagcgacgga       60

aagagtatga gctggaaaa                                                    79


<210>  105
<211>  83
<212>  DNA
<213>  Homo sapiens

<400>  105
ctttggaggc aagatataga tcttggagta agtcgagaag tatttgactt cagtcagcga       60

cggaaagagt atgagctgga aaa                                               83


<210>  106
<211>  81
<212>  DNA
<213>  Homo sapiens

<400>  106
ctttggaggc aagatataga ttggagtaag tggagaagta tttgacttca gtcagcgacg       60

gaaagagtat gagctggaaa a                                                 81


<210>  107
<211>  81
<212>  DNA
<213>  Homo sapiens

<400>  107
ctttggggca gatatagatc ttggagtaag tcgagaagta tttgacttca gtcagcgacg       60

gaaagagtat gagctggaaa a                                                 81


<210>  108
<211>  76
<212>  DNA
<213>  Homo sapiens

<400>  108
ctttggaggc aagatcttgg agtaagtcga gaagtatttg acttcagtca gcgacggaaa       60

gagtatgagc tggaaa                                                       76


<210>  109
<211>  79
<212>  DNA
<213>  Homo sapiens

<400>  109
ctttggaggc aagatataga ggagtaagtc gagaagtatt tgacttcagt cagcgacgga       60

aagagtatga gctggaaaa                                                    79


<210>  110
<211>  83
<212>  DNA
<213>  Homo sapiens

<400>  110
acatactttg gaggcaagat atagatcttg gagtaagtcg agaagtattt gacttcagtc       60

agcgacggaa agagtatgag ctg                                               83


<210>  111
<211>  83
<212>  DNA
<213>  Homo sapiens

<400>  111
acatactttg gaggcaagat atagatcttg gagtaagtgg agaagtattt gacttcagtc       60

agcgacggaa agagtatgag ctg                                               83


<210>  112
<211>  63
<212>  DNA
<213>  Homo sapiens

<400>  112
acatactttg gagtaagtcg agaagtattt gacttcagtc agcgacggaa agagtatgag       60

ctg                                                                     63


<210>  113
<211>  76
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA

<400>  113
gttttagagc tagaaatagc aagttaaaat aaggctagtc cgttatcaac ttgaaaaagt       60

ggcaccgagt cggtgc                                                       76


<210>  114
<211>  1367
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cas9

<400>  114

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  115
<211>  4101
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Cas9

<400>  115
gacaagaagt acagcatcgg cctggacatc ggcaccaact ctgtgggctg ggccgtgatc       60

accgacgagt acaaggtgcc cagcaagaaa ttcaaggtgc tgggcaacac cgaccggcac      120

agcatcaaga agaacctgat cggagccctg ctgttcgaca gcggcgaaac agccgaggcc      180

acccggctga agagaaccgc cagaagaaga tacaccagac ggaagaaccg gatctgctat      240

ctgcaagaga tcttcagcaa cgagatggcc aaggtggacg acagcttctt ccacagactg      300

gaagagtcct tcctggtgga agaggataag aagcacgagc ggcaccccat cttcggcaac      360

atcgtggacg aggtggccta ccacgagaag taccccacca tctaccacct gagaaagaaa      420

ctggtggaca gcaccgacaa ggccgacctg cggctgatct atctggccct ggcccacatg      480

atcaagttcc ggggccactt cctgatcgag ggcgacctga accccgacaa cagcgacgtg      540

gacaagctgt tcatccagct ggtgcagacc tacaaccagc tgttcgagga aaaccccatc      600

aacgccagcg gcgtggacgc caaggccatc ctgtctgcca gactgagcaa gagcagacgg      660

ctggaaaatc tgatcgccca gctgcccggc gagaagaaga atggcctgtt cggaaacctg      720

attgccctga gcctgggcct gacccccaac ttcaagagca acttcgacct ggccgaggat      780

gccaaactgc agctgagcaa ggacacctac gacgacgacc tggacaacct gctggcccag      840

atcggcgacc agtacgccga cctgtttctg gccgccaaga acctgtccga cgccatcctg      900

ctgagcgaca tcctgagagt gaacaccgag atcaccaagg cccccctgag cgcctctatg      960

atcaagagat acgacgagca ccaccaggac ctgaccctgc tgaaagctct cgtgcggcag     1020

cagctgcctg agaagtacaa agagattttc ttcgaccaga gcaagaacgg ctacgccggc     1080

tacattgacg gcggagccag ccaggaagag ttctacaagt tcatcaagcc catcctggaa     1140

aagatggacg gcaccgagga actgctcgtg aagctgaaca gagaggacct gctgcggaag     1200

cagcggacct tcgacaacgg cagcatcccc caccagatcc acctgggaga gctgcacgcc     1260

attctgcggc ggcaggaaga tttttaccca ttcctgaagg acaaccggga aaagatcgag     1320

aagatcctga ccttccgcat cccctactac gtgggccctc tggccagggg aaacagcaga     1380

ttcgcctgga tgaccagaaa gagcgaggaa accatcaccc cctggaactt cgaggaagtg     1440

gtggacaagg gcgcttccgc ccagagcttc atcgagcgga tgaccaactt cgataagaac     1500

ctgcccaacg agaaggtgct gcccaagcac agcctgctgt acgagtactt caccgtgtat     1560

aacgagctga ccaaagtgaa atacgtgacc gagggaatga gaaagcccgc cttcctgagc     1620

ggcgagcaga aaaaggccat cgtggacctg ctgttcaaga ccaaccggaa agtgaccgtg     1680

aagcagctga aagaggacta cttcaagaaa atcgagtgct tcgactccgt ggaaatctcc     1740

ggcgtggaag atcggttcaa cgcctccctg ggcacatacc acgatctgct gaaaattatc     1800

aaggacaagg acttcctgga caatgaggaa aacgaggaca ttctggaaga tatcgtgctg     1860

accctgacac tgtttgagga cagagagatg atcgaggaac ggctgaaaac ctatgcccac     1920

ctgttcgacg acaaagtgat gaagcagctg aagcggcgga gatacaccgg ctggggcagg     1980

ctgagccgga agctgatcaa cggcatccgg gacaagcagt ccggcaagac aatcctggat     2040

ttcctgaagt ccgacggctt cgccaacaga aacttcatgc agctgatcca cgacgacagc     2100

ctgaccttta aagaggacat ccagaaagcc caggtgtccg gccagggcga tagcctgcac     2160

gagcacattg ccaatctggc cggcagcccc gccattaaga agggcatcct gcagacagtg     2220

aaggtggtgg acgagctcgt gaaagtgatg ggccggcaca agcccgagaa catcgtgatc     2280

gaaatggcca gagagaacca gaccacccag aagggacaga agaacagccg cgagagaatg     2340

aagcggatcg aagagggcat caaagagctg ggcagccaga tcctgaaaga acaccccgtg     2400

gaaaacaccc agctgcagaa cgagaagctg tacctgtact acctgcagaa tgggcgggat     2460

atgtacgtgg accaggaact ggacatcaac cggctgtccg actacgatgt ggaccatatc     2520

gtgcctcaga gctttctgaa ggacgactcc atcgacaaca aggtgctgac cagaagcgac     2580

aagaaccggg gcaagagcga caacgtgccc tccgaagagg tcgtgaagaa gatgaagaac     2640

tactggcggc agctgctgaa cgccaagctg attacccaga gaaagttcga caatctgacc     2700

aaggccgaga gaggcggcct gagcgaactg gataaggccg gcttcatcaa gagacagctg     2760

gtggaaaccc ggcagatcac aaagcacgtg gcacagatcc tggactcccg gatgaacact     2820

aagtacgacg agaatgacaa gctgatccgg gaagtgaaag tgatcaccct gaagtccaag     2880

ctggtgtccg atttccggaa ggatttccag ttttacaaag tgcgcgagat caacaactac     2940

caccacgccc acgacgccta cctgaacgcc gtcgtgggaa ccgccctgat caaaaagtac     3000

cctaagctgg aaagcgagtt cgtgtacggc gactacaagg tgtacgacgt gcggaagatg     3060

atcgccaaga gcgagcagga aatcggcaag gctaccgcca agtacttctt ctacagcaac     3120

atcatgaact ttttcaagac cgagattacc ctggccaacg gcgagatccg gaagcggcct     3180

ctgatcgaga caaacggcga aaccggggag atcgtgtggg ataagggccg ggattttgcc     3240

accgtgcgga aagtgctgag catgccccaa gtgaatatcg tgaaaaagac cgaggtgcag     3300

acaggcggct tcagcaaaga gtctatcctg cccaagagga acagcgataa gctgatcgcc     3360

agaaagaagg actgggaccc taagaagtac ggcggcttcg acagccccac cgtggcctat     3420

tctgtgctgg tggtggccaa agtggaaaag ggcaagtcca agaaactgaa gagtgtgaaa     3480

gagctgctgg ggatcaccat catggaaaga agcagcttcg agaagaatcc catcgacttt     3540

ctggaagcca agggctacaa agaagtgaaa aaggacctga tcatcaagct gcctaagtac     3600

tccctgttcg agctggaaaa cggccggaag agaatgctgg cctctgccgg cgaactgcag     3660

aagggaaacg aactggccct gccctccaaa tatgtgaact tcctgtacct ggccagccac     3720

tatgagaagc tgaagggctc ccccgaggat aatgagcaga aacagctgtt tgtggaacag     3780

cacaagcact acctggacga gatcatcgag cagatcagcg agttctccaa gagagtgatc     3840

ctggccgacg ctaatctgga caaagtgctg tccgcctaca acaagcaccg ggataagccc     3900

atcagagagc aggccgagaa tatcatccac ctgtttaccc tgaccaatct gggagcccct     3960

gccgccttca agtactttga caccaccatc gaccggaaga ggtacaccag caccaaagag     4020

gtgctggacg ccaccctgat ccaccagagc atcaccggcc tgtacgagac acggatcgac     4080

ctgtctcagc tgggaggcga c                                               4101


<210>  116
<211>  39
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  minicmv promoter

<400>  116
ggtaggcgtg tacggtggga ggcctatata agcagagct                              39


<210>  117
<211>  212
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Ef1a promoter

<400>  117
gggcagagcg cacatcgccc acagtccccg agaagttggg gggaggggtc ggcaattgat       60

ccggtgccta gagaaggtgg cgcggggtaa actgggaaag tgatgtcgtg tactggctcc      120

gcctttttcc cgagggtggg ggagaaccgt atataagtgc agtagtcgcc gtgaacgttc      180

tttttcgcaa cgggtttgcc gccagaacac ag                                    212


<210>  118
<211>  241
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  U6 promoter

<400>  118
gagggcctat ttcccatgat tccttcatat ttgcatatac gatacaaggc tgttagagag       60

ataattggaa ttaatttgac tgtaaacaca aagatattag tacaaaatac gtgacgtaga      120

aagtaataat ttcttgggta gtttgcagtt ttaaaattat gttttaaaat ggactatcat      180

atgcttaccg taacttgaaa gtatttcgat ttcttggctt tatatatctt gtggaaagga      240

c                                                                      241


<210>  119
<211>  508
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CMV promoter

<400>  119
cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt       60

gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc attgacgtca      120

atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc      180

aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta      240

catgacctta tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac      300

catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg actcacgggg      360

atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc aaaatcaacg      420

ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg gtaggcgtgt      480

acggtgggag gtctatataa gcagagct                                         508


<210>  120
<211>  130
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AAV2 ITR

<400>  120
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct                                                             130


<210>  121
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  SV40 NLS

<400>  121
ccgaagaaaa agcgcaaggt c                                                 21

<210>  122
<211>  221
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  H1 promoter

<400>  122
gaacgctgac gtcatcaacc cgctccaagg aatcgcgggc ccagtgtcac taggcgggaa       60

cacccagcgc gcgtgcgccc tggcaggaag atggctgtga gggacagggg agtggcgccc      120

tgcaatattt gcatgtcgct atgtgttctg ggaaatcacc ataaacgtga aatgtctttg      180

gatttgggaa tcttataagt tctgtatgag accacagatc t                          221


<210>  123
<211>  267
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  7SK promoter

<400>  123
catatgccat gggctgccgc tctagactgc agtatttagc atgccccacc catctgcaag       60

gcattctgga tagtgtcaaa acagccggaa atcaagtccg tttatctcaa actttagcat      120

tttgggaata aatgatattt gctatgctgg ttaaattaga ttttagttaa atttcctgct      180

gaagctctag tacgataagt aacttgacct aagtgtaaag ttgagatttc cttcaggttt      240

atatagcttg tgcgccgcct gggtacc                                          267


<210>  124
<211>  96
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Full length guide RNA DNA sequence

<400>  124
gatatagatc ttggagtaag gttttagagc tagaaatagc aagttaaaat aaggctagtc       60

cgttatcaac ttgaaaaagt ggcaccgagt cggtgc                                 96


<210>  125
<211>  1041
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  guide RNA expression cassette

<400>  125
cgtgagggcc tatttcccat gattccttca tatttgcata tacgatacaa ggctgttaga       60

gagataattg gaattaattt gactgtaaac acaaagatat tagtacaaaa tacgtgacgt      120

agaaagtaat aatttcttgg gtagtttgca gttttaaaat tatgttttaa aatggactat      180

catatgctta ccgtaacttg aaagtatttc gatttcttgg ctttatatat cttgtggaaa      240

ggacgaaaca ccgatataga tcttggagta aggttttaga gctagaaata gcaagttaaa      300

ataaggctag tccgttatca acttgaaaaa gtggcaccga gtcggtgctt tttttgaacg      360

ctgacgtcat caacccgctc caaggaatcg cgggcccagt gtcactaggc gggaacaccc      420

agcgcgcgtg cgccctggca ggaagatggc tgtgagggac aggggagtgg cgccctgcaa      480

tatttgcatg tcgctatgtg ttctgggaaa tcaccataaa cgtgaaatgt ctttggattt      540

gggaatctta taagttctgt atgagaccac agatctgata tagatcttgg agtaaggttt      600

tagagctaga aatagcaagt taaaataagg ctagtccgtt atcaacttga aaaagtggca      660

ccgagtcggt gcttttttca tatgccatgg gctgccgctc tagactgcag tatttagcat      720

gccccaccca tctgcaaggc attctggata gtgtcaaaac agccggaaat caagtccgtt      780

tatctcaaac tttagcattt tgggaataaa tgatatttgc tatgctggtt aaattagatt      840

ttagttaaat ttcctgctga agctctagta cgataagtaa cttgacctaa gtgtaaagtt      900

gagatttcct tcaggtttat atagcttgtg cgccgcctgg gtaccgatat agatcttgga      960

gtaaggtttt agagctagaa atagcaagtt aaaataaggc tagtccgtta tcaacttgaa     1020

aaagtggcac cgagtcggtg c                                               1041


<210>  126
<211>  20
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  gRNA DNA binding domain

<400>  126
cuuacuccaa gaucuauauc                                                   20


<210>  127
<211>  76
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  RNA scaffold RNA sequence

<400>  127
gcaccgacuc ggugccacuu uuucaaguug auaacggacu agccuuauuu uaacuugcua       60

uuucuagcuc uaaaac                                                       76

<210>  128
<211>  96
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  guide RNA

<400>  128
cuuacuccaa gaucuauauc gcaccgacuc ggugccacuu uuucaaguug auaacggacu       60

agccuuauuu uaacuugcua uuucuagcuc uaaaac                                 96




