                         SEQUENCE LISTING

<110>  The University of Bristol
 
<120>  MATERIALS AND METHODS FOR MODULATING INTRAOCULAR AND INTRACRANIAL
        PRESSURE

<130>  007496581

<140>  PCT/EP2019/065231
<141>  2019-06-11

<150>  GB 1809588.5
<151>  2018-06-12

<160>  25    

<170>  PatentIn version 3.5

<210>  1
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  crRNA portion

<400>  1
gatgatgtac atgacagccc g                                                 21


<210>  2
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  crRNA portion

<400>  2
gatcgctact ctggcccaaa gt                                                22


<210>  3
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  crRNA portion

<400>  3
gatgtgaccc acactttggg c                                                 21


<210>  4
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  crRNA portion

<400>  4
tcttctggag ggctgtggtg g                                                 21


<210>  5
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  crRNA portion

<400>  5
accaatgctg atgaagacga a                                                 21


<210>  6
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  crRNA portion

<400>  6
tagggaggag gtgatgcccg a                                                 21


<210>  7
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA for use in targeting human AQP1

<400>  7
ctgagcatcg ccacgctggc g                                                 21


<210>  8
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA for use in targeting human AQP1

<400>  8
accgatgctg atgaagacaa a                                                 21


<210>  9
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  gRNA for use in targeting human AQP1

<400>  9
ccgccgtctg gttgttcccc a                                                 21


<210>  10
<211>  81
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  tracrRNA component from an sgRNA recognised by SaCas9

<400>  10
gttttagtac tctggaaaca gaatctacta aaacaaggca aaatgccgtg tttatctcgt       60

caacttgttg gcgagatttt t                                                 81


<210>  11
<211>  130
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  scAAV vectors

<400>  11
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct                                                             130


<210>  12
<211>  141
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  scAAV vector

<400>  12
aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg       60

ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc      120

gagcgcgcag ctgcctgcag g                                                141


<210>  13
<211>  736
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  "native" ShH10 VP1 sequence

<400>  13

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 
1               5                   10                  15      


Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 
            20                  25                  30          


Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 
        35                  40                  45              


Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 
    50                  55                  60                  


Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 
65                  70                  75                  80  


Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 
                85                  90                  95      


Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 
            100                 105                 110         


Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 
        115                 120                 125             


Phe Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 
    130                 135                 140                 


Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly 
145                 150                 155                 160 


Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 
                165                 170                 175     


Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro 
            180                 185                 190         


Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly 
        195                 200                 205             


Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala 
    210                 215                 220                 


Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile 
225                 230                 235                 240 


Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 
                245                 250                 255     


Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn His 
            260                 265                 270         


Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe 
        275                 280                 285             


His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn 
    290                 295                 300                 


Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Val Gln 
305                 310                 315                 320 


Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn 
                325                 330                 335     


Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro 
            340                 345                 350         


Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala 
        355                 360                 365             


Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly 
    370                 375                 380                 


Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro 
385                 390                 395                 400 


Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe 
                405                 410                 415     


Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp 
            420                 425                 430         


Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg 
        435                 440                 445             


Thr Gln Asp Gln Ser Gly Ser Ala Gln Asn Lys Asp Leu Leu Phe Ser 
    450                 455                 460                 


Arg Gly Ser Pro Ala Gly Met Ser Val Gln Pro Lys Asn Trp Leu Pro 
465                 470                 475                 480 


Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Lys Thr Asp Asn 
                485                 490                 495     


Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala Ser Lys Tyr Asn Leu Asn 
            500                 505                 510         


Gly Arg Glu Ser Ile Ile Asn Pro Gly Thr Ala Met Ala Ser His Lys 
        515                 520                 525             


Asp Asp Lys Asn Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe Gly 
    530                 535                 540                 


Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala Leu Asp Asn Val Met Ile 
545                 550                 555                 560 


Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Arg 
                565                 570                 575     


Phe Gly Thr Val Ala Val Asn Leu Gln Ser Ser Ser Thr Asp Pro Ala 
            580                 585                 590         


Thr Gly Asp Val His Val Met Gly Ala Leu Pro Gly Met Val Trp Gln 
        595                 600                 605             


Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His 
    610                 615                 620                 


Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu 
625                 630                 635                 640 


Lys Asn Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 
                645                 650                 655     


Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys Phe Ala Ser Phe Ile Thr 
            660                 665                 670         


Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln 
        675                 680                 685             


Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Val Gln Tyr Thr Ser Asn 
    690                 695                 700                 


Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr Val Asp Asn Asn Gly Leu 
705                 710                 715                 720 


Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu 
                725                 730                 735     


<210>  14
<211>  599
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VP2 native sequence

<400>  14

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


Asp Ser Ser Ser Gly Ile Gly Lys Thr Gly Gln Gln Pro Ala Lys Lys 
            20                  25                  30          


Arg Leu Asn Phe Gly Gln Thr Gly Asp Ser Glu Ser Val Pro Asp Pro 
        35                  40                  45              


Gln Pro Leu Gly Glu Pro Pro Ala Thr Pro Ala Ala Val Gly Pro Thr 
    50                  55                  60                  


Thr Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly 
65                  70                  75                  80  


Ala Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr 
                85                  90                  95      


Trp Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu 
            100                 105                 110         


Pro Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr 
        115                 120                 125             


Gly Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly 
    130                 135                 140                 


Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp 
145                 150                 155                 160 


Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn 
                165                 170                 175     


Phe Lys Leu Phe Asn Val Gln Val Lys Glu Val Thr Thr Asn Asp Gly 
            180                 185                 190         


Val Thr Thr Ile Ala Asn Asn Leu Thr Ser Thr Val Gln Val Phe Ser 
        195                 200                 205             


Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly 
    210                 215                 220                 


Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly 
225                 230                 235                 240 


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


Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn 
            260                 265                 270         


Phe Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr 
        275                 280                 285             


Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln 
    290                 295                 300                 


Tyr Leu Tyr Tyr Leu Asn Arg Thr Gln Asp Gln Ser Gly Ser Ala Gln 
305                 310                 315                 320 


Asn Lys Asp Leu Leu Phe Ser Arg Gly Ser Pro Ala Gly Met Ser Val 
                325                 330                 335     


Gln Pro Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val 
            340                 345                 350         


Ser Lys Thr Lys Thr Asp Asn Asn Asn Ser Asn Phe Thr Trp Thr Gly 
        355                 360                 365             


Ala Ser Lys Tyr Asn Leu Asn Gly Arg Glu Ser Ile Ile Asn Pro Gly 
    370                 375                 380                 


Thr Ala Met Ala Ser His Lys Asp Asp Lys Asn Lys Phe Phe Pro Met 
385                 390                 395                 400 


Ser Gly Val Met Ile Phe Gly Lys Glu Ser Ala Gly Ala Ser Asn Thr 
                405                 410                 415     


Ala Leu Asp Asn Val Met Ile Thr Asp Glu Glu Glu Ile Lys Ala Thr 
            420                 425                 430         


Asn Pro Val Ala Thr Glu Arg Phe Gly Thr Val Ala Val Asn Leu Gln 
        435                 440                 445             


Ser Ser Ser Thr Asp Pro Ala Thr Gly Asp Val His Val Met Gly Ala 
    450                 455                 460                 


Leu Pro Gly Met Val Trp Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro 
465                 470                 475                 480 


Ile Trp Ala Lys Ile Pro His Thr Asp Gly His Phe His Pro Ser Pro 
                485                 490                 495     


Leu Met Gly Gly Phe Gly Leu Lys Asn Pro Pro Pro Gln Ile Leu Ile 
            500                 505                 510         


Lys Asn Thr Pro Val Pro Ala Asn Pro Pro Ala Glu Phe Ser Ala Thr 
        515                 520                 525             


Lys Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val 
    530                 535                 540                 


Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro 
545                 550                 555                 560 


Glu Val Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Ala Asn Val Asp Phe 
                565                 570                 575     


Thr Val Asp Asn Asn Gly Leu Tyr Thr Glu Pro Arg Pro Ile Gly Thr 
            580                 585                 590         


Arg Tyr Leu Thr Arg Pro Leu 
        595                 


<210>  15
<211>  534
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VP3 native sequence

<400>  15

Met Ala Ser Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala 
1               5                   10                  15      


Asp Gly Val Gly Asn Ala Ser Gly Asn Trp His Cys Asp Ser Thr Trp 
            20                  25                  30          


Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro 
        35                  40                  45              


Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly 
    50                  55                  60                  


Ala Ser Asn Asp Asn His Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr 
65                  70                  75                  80  


Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln 
                85                  90                  95      


Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe 
            100                 105                 110         


Lys Leu Phe Asn Val Gln Val Lys Glu Val Thr Thr Asn Asp Gly Val 
        115                 120                 125             


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


Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys 
145                 150                 155                 160 


Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr 
                165                 170                 175     


Leu Thr Leu Asn Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr 
            180                 185                 190         


Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe 
        195                 200                 205             


Thr Phe Ser Tyr Thr Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala 
    210                 215                 220                 


His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr 
225                 230                 235                 240 


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


Lys Asp Leu Leu Phe Ser Arg Gly Ser Pro Ala Gly Met Ser Val Gln 
            260                 265                 270         


Pro Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser 
        275                 280                 285             


Lys Thr Lys Thr Asp Asn Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala 
    290                 295                 300                 


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


Ala Met Ala Ser His Lys Asp Asp Lys Asn Lys Phe Phe Pro Met Ser 
                325                 330                 335     


Gly Val Met Ile Phe Gly Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala 
            340                 345                 350         


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


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


Ser Ser Thr Asp Pro Ala Thr Gly Asp Val His Val Met Gly Ala Leu 
385                 390                 395                 400 


Pro Gly Met Val Trp Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile 
                405                 410                 415     


Trp Ala Lys Ile Pro His Thr Asp Gly His Phe His Pro Ser Pro Leu 
            420                 425                 430         


Met Gly Gly Phe Gly Leu Lys Asn Pro Pro Pro Gln Ile Leu Ile Lys 
        435                 440                 445             


Asn Thr Pro Val Pro Ala Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys 
    450                 455                 460                 


Phe Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu 
465                 470                 475                 480 


Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu 
                485                 490                 495     


Val Gln Tyr Thr Ser Asn Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr 
            500                 505                 510         


Val Asp Asn Asn Gly Leu Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg 
        515                 520                 525             


Tyr Leu Thr Arg Pro Leu 
    530                 


<210>  16
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Mouse Aquaporin 1 Exon 1-1B

<400>  16
gatgatgtac atgacagccc g                                                 21


<210>  17
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Mouse Aquaporin 1 Exon 1-1E

<400>  17
atcgctactc tggcccaaag t                                                 21


<210>  18
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer

<400>  18
ggaggaactg ctggcatgca cc                                                22


<210>  19
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer

<400>  19
ctagagtgcc agcctctgcc ct                                                22


<210>  20
<211>  7448
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AAV-SaCas9 plasmid mAqp1 exon 1 guide 1B

<400>  20
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct gcggcctcta gactcgaggc gttgacattg attattgact agttattaat      180

agtaatcaat tacggggtca ttagttcata gcccatatat ggagttccgc gttacataac      240

ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc ccgcccattg acgtcaataa      300

tgacgtatgt tcccatagta acgccaatag ggactttcca ttgacgtcaa tgggtggagt      360

atttacggta aactgcccac ttggcagtac atcaagtgta tcatatgcca agtacgcccc      420

ctattgacgt caatgacggt aaatggcccg cctggcatta tgcccagtac atgaccttat      480

gggactttcc tacttggcag tacatctacg tattagtcat cgctattacc atggtgatgc      540

ggttttggca gtacatcaat gggcgtggat agcggtttga ctcacgggga tttccaagtc      600

tccaccccat tgacgtcaat gggagtttgt tttggcacca aaatcaacgg gactttccaa      660

aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg taggcgtgta cggtgggagg      720

tctatataag cagagctctc tggctaacta ccggtgccac catggcccca aagaagaagc      780

ggaaggtcgg tatccacgga gtcccagcag ccaagcggaa ctacatcctg ggcctggaca      840

tcggcatcac cagcgtgggc tacggcatca tcgactacga gacacgggac gtgatcgatg      900

ccggcgtgcg gctgttcaaa gaggccaacg tggaaaacaa cgagggcagg cggagcaaga      960

gaggcgccag aaggctgaag cggcggaggc ggcatagaat ccagagagtg aagaagctgc     1020

tgttcgacta caacctgctg accgaccaca gcgagctgag cggcatcaac ccctacgagg     1080

ccagagtgaa gggcctgagc cagaagctga gcgaggaaga gttctctgcc gccctgctgc     1140

acctggccaa gagaagaggc gtgcacaacg tgaacgaggt ggaagaggac accggcaacg     1200

agctgtccac caaagagcag atcagccgga acagcaaggc cctggaagag aaatacgtgg     1260

ccgaactgca gctggaacgg ctgaagaaag acggcgaagt gcggggcagc atcaacagat     1320

tcaagaccag cgactacgtg aaagaagcca aacagctgct gaaggtgcag aaggcctacc     1380

accagctgga ccagagcttc atcgacacct acatcgacct gctggaaacc cggcggacct     1440

actatgaggg acctggcgag ggcagcccct tcggctggaa ggacatcaaa gaatggtacg     1500

agatgctgat gggccactgc acctacttcc ccgaggaact gcggagcgtg aagtacgcct     1560

acaacgccga cctgtacaac gccctgaacg acctgaacaa tctcgtgatc accagggacg     1620

agaacgagaa gctggaatat tacgagaagt tccagatcat cgagaacgtg ttcaagcaga     1680

agaagaagcc caccctgaag cagatcgcca aagaaatcct cgtgaacgaa gaggatatta     1740

agggctacag agtgaccagc accggcaagc ccgagttcac caacctgaag gtgtaccacg     1800

acatcaagga cattaccgcc cggaaagaga ttattgagaa cgccgagctg ctggatcaga     1860

ttgccaagat cctgaccatc taccagagca gcgaggacat ccaggaagaa ctgaccaatc     1920

tgaactccga gctgacccag gaagagatcg agcagatctc taatctgaag ggctataccg     1980

gcacccacaa cctgagcctg aaggccatca acctgatcct ggacgagctg tggcacacca     2040

acgacaacca gatcgctatc ttcaaccggc tgaagctggt gcccaagaag gtggacctgt     2100

cccagcagaa agagatcccc accaccctgg tggacgactt catcctgagc cccgtcgtga     2160

agagaagctt catccagagc atcaaagtga tcaacgccat catcaagaag tacggcctgc     2220

ccaacgacat cattatcgag ctggcccgcg agaagaactc caaggacgcc cagaaaatga     2280

tcaacgagat gcagaagcgg aaccggcaga ccaacgagcg gatcgaggaa atcatccgga     2340

ccaccggcaa agagaacgcc aagtacctga tcgagaagat caagctgcac gacatgcagg     2400

aaggcaagtg cctgtacagc ctggaagcca tccctctgga agatctgctg aacaacccct     2460

tcaactatga ggtggaccac atcatcccca gaagcgtgtc cttcgacaac agcttcaaca     2520

acaaggtgct cgtgaagcag gaagaaaaca gcaagaaggg caaccggacc ccattccagt     2580

acctgagcag cagcgacagc aagatcagct acgaaacctt caagaagcac atcctgaatc     2640

tggccaaggg caagggcaga atcagcaaga ccaagaaaga gtatctgctg gaagaacggg     2700

acatcaacag gttctccgtg cagaaagact tcatcaaccg gaacctggtg gataccagat     2760

acgccaccag aggcctgatg aacctgctgc ggagctactt cagagtgaac aacctggacg     2820

tgaaagtgaa gtccatcaat ggcggcttca ccagctttct gcggcggaag tggaagttta     2880

agaaagagcg gaacaagggg tacaagcacc acgccgagga cgccctgatc attgccaacg     2940

ccgatttcat cttcaaagag tggaagaaac tggacaaggc caaaaaagtg atggaaaacc     3000

agatgttcga ggaaaagcag gccgagagca tgcccgagat cgaaaccgag caggagtaca     3060

aagagatctt catcaccccc caccagatca agcacattaa ggacttcaag gactacaagt     3120

acagccaccg ggtggacaag aagcctaata gagagctgat taacgacacc ctgtactcca     3180

cccggaagga cgacaagggc aacaccctga tcgtgaacaa tctgaacggc ctgtacgaca     3240

aggacaatga caagctgaaa aagctgatca acaagagccc cgaaaagctg ctgatgtacc     3300

accacgaccc ccagacctac cagaaactga agctgattat ggaacagtac ggcgacgaga     3360

agaatcccct gtacaagtac tacgaggaaa ccgggaacta cctgaccaag tactccaaaa     3420

aggacaacgg ccccgtgatc aagaagatta agtattacgg caacaaactg aacgcccatc     3480

tggacatcac cgacgactac cccaacagca gaaacaaggt cgtgaagctg tccctgaagc     3540

cctacagatt cgacgtgtac ctggacaatg gcgtgtacaa gttcgtgacc gtgaagaatc     3600

tggatgtgat caaaaaagaa aactactacg aagtgaatag caagtgctat gaggaagcta     3660

agaagctgaa gaagatcagc aaccaggccg agtttatcgc ctccttctac aacaacgatc     3720

tgatcaagat caacggcgag ctgtatagag tgatcggcgt gaacaacgac ctgctgaacc     3780

ggatcgaagt gaacatgatc gacatcacct accgcgagta cctggaaaac atgaacgaca     3840

agaggccccc caggatcatt aagacaatcg cctccaagac ccagagcatt aagaagtaca     3900

gcacagacat tctgggcaac ctgtatgaag tgaaatctaa gaagcaccct cagatcatca     3960

aaaagggcaa aaggccggcg gccacgaaaa aggccggcca ggcaaaaaag aaaaagggat     4020

cctacccata cgatgttcca gattacgctt acccatacga tgttccagat tacgcttacc     4080

catacgatgt tccagattac gcttaagaat tcctagagct cgctgatcag cctcgactgt     4140

gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga     4200

aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag     4260

taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga     4320

agagaatagc aggcatgctg gggaggtacc tgagggccta tttcccatga ttccttcata     4380

tttgcatata cgatacaagg ctgttagaga gataattgga attaatttga ctgtaaacac     4440

aaagatatta gtacaaaata cgtgacgtag aaagtaataa tttcttgggt agtttgcagt     4500

tttaaaatta tgttttaaaa tggactatca tatgcttacc gtaacttgaa agtatttcga     4560

tttcttggct ttatatatct tgtggaaagg acgaaacacc gatgatgtac atgacagccc     4620

ggttttagta ctctggaaac agaatctact aaaacaaggc aaaatgccgt gtttatctcg     4680

tcaacttgtt ggcgagattt ttgcggccgc aggaacccct agtgatggag ttggccactc     4740

cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc cgacgcccgg     4800

gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag ctgcctgcag gggcgcctga     4860

tgcggtattt tctccttacg catctgtgcg gtatttcaca ccgcatacgt caaagcaacc     4920

atagtacgcg ccctgtagcg gcgcattaag cgcggcgggt gtggtggtta cgcgcagcgt     4980

gaccgctaca cttgccagcg ccctagcgcc cgctcctttc gctttcttcc cttcctttct     5040

cgccacgttc gccggctttc cccgtcaagc tctaaatcgg gggctccctt tagggttccg     5100

atttagtgct ttacggcacc tcgaccccaa aaaacttgat ttgggtgatg gttcacgtag     5160

tgggccatcg ccctgataga cggtttttcg ccctttgacg ttggagtcca cgttctttaa     5220

tagtggactc ttgttccaaa ctggaacaac actcaaccct atctcgggct attcttttga     5280

tttataaggg attttgccga tttcggccta ttggttaaaa aatgagctga tttaacaaaa     5340

atttaacgcg aattttaaca aaatattaac gtttacaatt ttatggtgca ctctcagtac     5400

aatctgctct gatgccgcat agttaagcca gccccgacac ccgccaacac ccgctgacgc     5460

gccctgacgg gcttgtctgc tcccggcatc cgcttacaga caagctgtga ccgtctccgg     5520

gagctgcatg tgtcagaggt tttcaccgtc atcaccgaaa cgcgcgagac gaaagggcct     5580

cgtgatacgc ctatttttat aggttaatgt catgataata atggtttctt agacgtcagg     5640

tggcactttt cggggaaatg tgcgcggaac ccctatttgt ttatttttct aaatacattc     5700

aaatatgtat ccgctcatga gacaataacc ctgataaatg cttcaataat attgaaaaag     5760

gaagagtatg agtattcaac atttccgtgt cgcccttatt cccttttttg cggcattttg     5820

ccttcctgtt tttgctcacc cagaaacgct ggtgaaagta aaagatgctg aagatcagtt     5880

gggtgcacga gtgggttaca tcgaactgga tctcaacagc ggtaagatcc ttgagagttt     5940

tcgccccgaa gaacgttttc caatgatgag cacttttaaa gttctgctat gtggcgcggt     6000

attatcccgt attgacgccg ggcaagagca actcggtcgc cgcatacact attctcagaa     6060

tgacttggtt gagtactcac cagtcacaga aaagcatctt acggatggca tgacagtaag     6120

agaattatgc agtgctgcca taaccatgag tgataacact gcggccaact tacttctgac     6180

aacgatcgga ggaccgaagg agctaaccgc ttttttgcac aacatggggg atcatgtaac     6240

tcgccttgat cgttgggaac cggagctgaa tgaagccata ccaaacgacg agcgtgacac     6300

cacgatgcct gtagcaatgg caacaacgtt gcgcaaacta ttaactggcg aactacttac     6360

tctagcttcc cggcaacaat taatagactg gatggaggcg gataaagttg caggaccact     6420

tctgcgctcg gcccttccgg ctggctggtt tattgctgat aaatctggag ccggtgagcg     6480

tggaagccgc ggtatcattg cagcactggg gccagatggt aagccctccc gtatcgtagt     6540

tatctacacg acggggagtc aggcaactat ggatgaacga aatagacaga tcgctgagat     6600

aggtgcctca ctgattaagc attggtaact gtcagaccaa gtttactcat atatacttta     6660

gattgattta aaacttcatt tttaatttaa aaggatctag gtgaagatcc tttttgataa     6720

tctcatgacc aaaatccctt aacgtgagtt ttcgttccac tgagcgtcag accccgtaga     6780

aaagatcaaa ggatcttctt gagatccttt ttttctgcgc gtaatctgct gcttgcaaac     6840

aaaaaaacca ccgctaccag cggtggtttg tttgccggat caagagctac caactctttt     6900

tccgaaggta actggcttca gcagagcgca gataccaaat actgtccttc tagtgtagcc     6960

gtagttaggc caccacttca agaactctgt agcaccgcct acatacctcg ctctgctaat     7020

cctgttacca gtggctgctg ccagtggcga taagtcgtgt cttaccgggt tggactcaag     7080

acgatagtta ccggataagg cgcagcggtc gggctgaacg gggggttcgt gcacacagcc     7140

cagcttggag cgaacgacct acaccgaact gagataccta cagcgtgagc tatgagaaag     7200

cgccacgctt cccgaaggga gaaaggcgga caggtatccg gtaagcggca gggtcggaac     7260

aggagagcgc acgagggagc ttccaggggg aaacgcctgg tatctttata gtcctgtcgg     7320

gtttcgccac ctctgacttg agcgtcgatt tttgtgatgc tcgtcagggg ggcggagcct     7380

atggaaaaac gccagcaacg cggccttttt acggttcctg gccttttgct ggccttttgc     7440

tcacatgt                                                              7448


<210>  21
<211>  7449
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AAV-SaCas9 plasmid mAqp1 exon 1 guide 1E

<400>  21
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct gcggcctcta gactcgaggc gttgacattg attattgact agttattaat      180

agtaatcaat tacggggtca ttagttcata gcccatatat ggagttccgc gttacataac      240

ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc ccgcccattg acgtcaataa      300

tgacgtatgt tcccatagta acgccaatag ggactttcca ttgacgtcaa tgggtggagt      360

atttacggta aactgcccac ttggcagtac atcaagtgta tcatatgcca agtacgcccc      420

ctattgacgt caatgacggt aaatggcccg cctggcatta tgcccagtac atgaccttat      480

gggactttcc tacttggcag tacatctacg tattagtcat cgctattacc atggtgatgc      540

ggttttggca gtacatcaat gggcgtggat agcggtttga ctcacgggga tttccaagtc      600

tccaccccat tgacgtcaat gggagtttgt tttggcacca aaatcaacgg gactttccaa      660

aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg taggcgtgta cggtgggagg      720

tctatataag cagagctctc tggctaacta ccggtgccac catggcccca aagaagaagc      780

ggaaggtcgg tatccacgga gtcccagcag ccaagcggaa ctacatcctg ggcctggaca      840

tcggcatcac cagcgtgggc tacggcatca tcgactacga gacacgggac gtgatcgatg      900

ccggcgtgcg gctgttcaaa gaggccaacg tggaaaacaa cgagggcagg cggagcaaga      960

gaggcgccag aaggctgaag cggcggaggc ggcatagaat ccagagagtg aagaagctgc     1020

tgttcgacta caacctgctg accgaccaca gcgagctgag cggcatcaac ccctacgagg     1080

ccagagtgaa gggcctgagc cagaagctga gcgaggaaga gttctctgcc gccctgctgc     1140

acctggccaa gagaagaggc gtgcacaacg tgaacgaggt ggaagaggac accggcaacg     1200

agctgtccac caaagagcag atcagccgga acagcaaggc cctggaagag aaatacgtgg     1260

ccgaactgca gctggaacgg ctgaagaaag acggcgaagt gcggggcagc atcaacagat     1320

tcaagaccag cgactacgtg aaagaagcca aacagctgct gaaggtgcag aaggcctacc     1380

accagctgga ccagagcttc atcgacacct acatcgacct gctggaaacc cggcggacct     1440

actatgaggg acctggcgag ggcagcccct tcggctggaa ggacatcaaa gaatggtacg     1500

agatgctgat gggccactgc acctacttcc ccgaggaact gcggagcgtg aagtacgcct     1560

acaacgccga cctgtacaac gccctgaacg acctgaacaa tctcgtgatc accagggacg     1620

agaacgagaa gctggaatat tacgagaagt tccagatcat cgagaacgtg ttcaagcaga     1680

agaagaagcc caccctgaag cagatcgcca aagaaatcct cgtgaacgaa gaggatatta     1740

agggctacag agtgaccagc accggcaagc ccgagttcac caacctgaag gtgtaccacg     1800

acatcaagga cattaccgcc cggaaagaga ttattgagaa cgccgagctg ctggatcaga     1860

ttgccaagat cctgaccatc taccagagca gcgaggacat ccaggaagaa ctgaccaatc     1920

tgaactccga gctgacccag gaagagatcg agcagatctc taatctgaag ggctataccg     1980

gcacccacaa cctgagcctg aaggccatca acctgatcct ggacgagctg tggcacacca     2040

acgacaacca gatcgctatc ttcaaccggc tgaagctggt gcccaagaag gtggacctgt     2100

cccagcagaa agagatcccc accaccctgg tggacgactt catcctgagc cccgtcgtga     2160

agagaagctt catccagagc atcaaagtga tcaacgccat catcaagaag tacggcctgc     2220

ccaacgacat cattatcgag ctggcccgcg agaagaactc caaggacgcc cagaaaatga     2280

tcaacgagat gcagaagcgg aaccggcaga ccaacgagcg gatcgaggaa atcatccgga     2340

ccaccggcaa agagaacgcc aagtacctga tcgagaagat caagctgcac gacatgcagg     2400

aaggcaagtg cctgtacagc ctggaagcca tccctctgga agatctgctg aacaacccct     2460

tcaactatga ggtggaccac atcatcccca gaagcgtgtc cttcgacaac agcttcaaca     2520

acaaggtgct cgtgaagcag gaagaaaaca gcaagaaggg caaccggacc ccattccagt     2580

acctgagcag cagcgacagc aagatcagct acgaaacctt caagaagcac atcctgaatc     2640

tggccaaggg caagggcaga atcagcaaga ccaagaaaga gtatctgctg gaagaacggg     2700

acatcaacag gttctccgtg cagaaagact tcatcaaccg gaacctggtg gataccagat     2760

acgccaccag aggcctgatg aacctgctgc ggagctactt cagagtgaac aacctggacg     2820

tgaaagtgaa gtccatcaat ggcggcttca ccagctttct gcggcggaag tggaagttta     2880

agaaagagcg gaacaagggg tacaagcacc acgccgagga cgccctgatc attgccaacg     2940

ccgatttcat cttcaaagag tggaagaaac tggacaaggc caaaaaagtg atggaaaacc     3000

agatgttcga ggaaaagcag gccgagagca tgcccgagat cgaaaccgag caggagtaca     3060

aagagatctt catcaccccc caccagatca agcacattaa ggacttcaag gactacaagt     3120

acagccaccg ggtggacaag aagcctaata gagagctgat taacgacacc ctgtactcca     3180

cccggaagga cgacaagggc aacaccctga tcgtgaacaa tctgaacggc ctgtacgaca     3240

aggacaatga caagctgaaa aagctgatca acaagagccc cgaaaagctg ctgatgtacc     3300

accacgaccc ccagacctac cagaaactga agctgattat ggaacagtac ggcgacgaga     3360

agaatcccct gtacaagtac tacgaggaaa ccgggaacta cctgaccaag tactccaaaa     3420

aggacaacgg ccccgtgatc aagaagatta agtattacgg caacaaactg aacgcccatc     3480

tggacatcac cgacgactac cccaacagca gaaacaaggt cgtgaagctg tccctgaagc     3540

cctacagatt cgacgtgtac ctggacaatg gcgtgtacaa gttcgtgacc gtgaagaatc     3600

tggatgtgat caaaaaagaa aactactacg aagtgaatag caagtgctat gaggaagcta     3660

agaagctgaa gaagatcagc aaccaggccg agtttatcgc ctccttctac aacaacgatc     3720

tgatcaagat caacggcgag ctgtatagag tgatcggcgt gaacaacgac ctgctgaacc     3780

ggatcgaagt gaacatgatc gacatcacct accgcgagta cctggaaaac atgaacgaca     3840

agaggccccc caggatcatt aagacaatcg cctccaagac ccagagcatt aagaagtaca     3900

gcacagacat tctgggcaac ctgtatgaag tgaaatctaa gaagcaccct cagatcatca     3960

aaaagggcaa aaggccggcg gccacgaaaa aggccggcca ggcaaaaaag aaaaagggat     4020

cctacccata cgatgttcca gattacgctt acccatacga tgttccagat tacgcttacc     4080

catacgatgt tccagattac gcttaagaat tcctagagct cgctgatcag cctcgactgt     4140

gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga     4200

aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag     4260

taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga     4320

agagaatagc aggcatgctg gggaggtacc tgagggccta tttcccatga ttccttcata     4380

tttgcatata cgatacaagg ctgttagaga gataattgga attaatttga ctgtaaacac     4440

aaagatatta gtacaaaata cgtgacgtag aaagtaataa tttcttgggt agtttgcagt     4500

tttaaaatta tgttttaaaa tggactatca tatgcttacc gtaacttgaa agtatttcga     4560

tttcttggct ttatatatct tgtggaaagg acgaaacacc gatcgctact ctggcccaaa     4620

gtgttttagt actctggaaa cagaatctac taaaacaagg caaaatgccg tgtttatctc     4680

gtcaacttgt tggcgagatt tttgcggccg caggaacccc tagtgatgga gttggccact     4740

ccctctctgc gcgctcgctc gctcactgag gccgggcgac caaaggtcgc ccgacgcccg     4800

ggctttgccc gggcggcctc agtgagcgag cgagcgcgca gctgcctgca ggggcgcctg     4860

atgcggtatt ttctccttac gcatctgtgc ggtatttcac accgcatacg tcaaagcaac     4920

catagtacgc gccctgtagc ggcgcattaa gcgcggcggg tgtggtggtt acgcgcagcg     4980

tgaccgctac acttgccagc gccctagcgc ccgctccttt cgctttcttc ccttcctttc     5040

tcgccacgtt cgccggcttt ccccgtcaag ctctaaatcg ggggctccct ttagggttcc     5100

gatttagtgc tttacggcac ctcgacccca aaaaacttga tttgggtgat ggttcacgta     5160

gtgggccatc gccctgatag acggtttttc gccctttgac gttggagtcc acgttcttta     5220

atagtggact cttgttccaa actggaacaa cactcaaccc tatctcgggc tattcttttg     5280

atttataagg gattttgccg atttcggcct attggttaaa aaatgagctg atttaacaaa     5340

aatttaacgc gaattttaac aaaatattaa cgtttacaat tttatggtgc actctcagta     5400

caatctgctc tgatgccgca tagttaagcc agccccgaca cccgccaaca cccgctgacg     5460

cgccctgacg ggcttgtctg ctcccggcat ccgcttacag acaagctgtg accgtctccg     5520

ggagctgcat gtgtcagagg ttttcaccgt catcaccgaa acgcgcgaga cgaaagggcc     5580

tcgtgatacg cctattttta taggttaatg tcatgataat aatggtttct tagacgtcag     5640

gtggcacttt tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt     5700

caaatatgta tccgctcatg agacaataac cctgataaat gcttcaataa tattgaaaaa     5760

ggaagagtat gagtattcaa catttccgtg tcgcccttat tccctttttt gcggcatttt     5820

gccttcctgt ttttgctcac ccagaaacgc tggtgaaagt aaaagatgct gaagatcagt     5880

tgggtgcacg agtgggttac atcgaactgg atctcaacag cggtaagatc cttgagagtt     5940

ttcgccccga agaacgtttt ccaatgatga gcacttttaa agttctgcta tgtggcgcgg     6000

tattatcccg tattgacgcc gggcaagagc aactcggtcg ccgcatacac tattctcaga     6060

atgacttggt tgagtactca ccagtcacag aaaagcatct tacggatggc atgacagtaa     6120

gagaattatg cagtgctgcc ataaccatga gtgataacac tgcggccaac ttacttctga     6180

caacgatcgg aggaccgaag gagctaaccg cttttttgca caacatgggg gatcatgtaa     6240

ctcgccttga tcgttgggaa ccggagctga atgaagccat accaaacgac gagcgtgaca     6300

ccacgatgcc tgtagcaatg gcaacaacgt tgcgcaaact attaactggc gaactactta     6360

ctctagcttc ccggcaacaa ttaatagact ggatggaggc ggataaagtt gcaggaccac     6420

ttctgcgctc ggcccttccg gctggctggt ttattgctga taaatctgga gccggtgagc     6480

gtggaagccg cggtatcatt gcagcactgg ggccagatgg taagccctcc cgtatcgtag     6540

ttatctacac gacggggagt caggcaacta tggatgaacg aaatagacag atcgctgaga     6600

taggtgcctc actgattaag cattggtaac tgtcagacca agtttactca tatatacttt     6660

agattgattt aaaacttcat ttttaattta aaaggatcta ggtgaagatc ctttttgata     6720

atctcatgac caaaatccct taacgtgagt tttcgttcca ctgagcgtca gaccccgtag     6780

aaaagatcaa aggatcttct tgagatcctt tttttctgcg cgtaatctgc tgcttgcaaa     6840

caaaaaaacc accgctacca gcggtggttt gtttgccgga tcaagagcta ccaactcttt     6900

ttccgaaggt aactggcttc agcagagcgc agataccaaa tactgtcctt ctagtgtagc     6960

cgtagttagg ccaccacttc aagaactctg tagcaccgcc tacatacctc gctctgctaa     7020

tcctgttacc agtggctgct gccagtggcg ataagtcgtg tcttaccggg ttggactcaa     7080

gacgatagtt accggataag gcgcagcggt cgggctgaac ggggggttcg tgcacacagc     7140

ccagcttgga gcgaacgacc tacaccgaac tgagatacct acagcgtgag ctatgagaaa     7200

gcgccacgct tcccgaaggg agaaaggcgg acaggtatcc ggtaagcggc agggtcggaa     7260

caggagagcg cacgagggag cttccagggg gaaacgcctg gtatctttat agtcctgtcg     7320

ggtttcgcca cctctgactt gagcgtcgat ttttgtgatg ctcgtcaggg gggcggagcc     7380

tatggaaaaa cgccagcaac gcggcctttt tacggttcct ggccttttgc tggccttttg     7440

ctcacatgt                                                             7449


<210>  22
<211>  510
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  exon 1 of mouse Aqp1

<400>  22
aataggccca gcccaggctg tggctcagct cttggaggga gttgagcacc aggcatccag       60

cggttaagtc gaggtccctg ccagcatggc cagtgaaatc aagaagaagc tcttctggag      120

ggctgtggtg gctgagttcc tggccatgac cctcttcgtc ttcatcagca ttggttctgc      180

cctaggcttc aattacccac tggagagaaa ccagacgctg gtccaggaca acgtgaaggt      240

gtcgctggcc tttggtttga gcatcgctac tctggcccaa agtgtgggtc acatcagcgg      300

tgctcacctc aaccctgcgg tcacactggg gctcctgctc agctgtcaga tcagcatcct      360

ccgggctgtc atgtacatca tcgcccagtg tgtgggagcc atcgtcgcca cggccattct      420

ctcgggcatc acctcctccc tagtcgacaa ttcacttggc cgcaatgacg tgagtggggt      480

atcttaggct tagggtgtct gtaggagaag                                       510


<210>  23
<211>  168
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  genomic DNA alteratiosn sequenced from Mix sgRNA treated B6-RPE 
       cells

<400>  23
aggtgtcgct ggcctttggt ttgagcatcg ctactctggc ccaaagtgtg ggtcacatca       60

gcggtgctca cctcaaccct gcggtcacac tggggctcct gctcagctgt cagatcagca      120

tcctccgggc tgtcatgtac atcatcgccc agtgtgtggg agccatcg                   168


<210>  24
<211>  84
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  genomic DNA alteratiosn sequenced from Mix sgRNA treated B6-RPE 
       cells

<400>  24
aggtgtcgct ggcctttggt ttgagcatcg ctactctggc ccaagctgtc atgtacatca       60

tcgcccagtg tgtgggagcc atcg                                              84


<210>  25
<211>  169
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  genomic DNA alteratiosn sequenced from Mix sgRNA treated B6-RPE 
       cells

<400>  25
aggtgtcgct ggcctttggt ttgagcatcg ctactctggc ccaaagtgtg ggtcacatca       60

gcggtgctca cctcaaccct gcggtcacac tggggctcct gctcagctgt cagatcagca      120

tcctccggcg ctgtcatgta catcatcgcc cagtgtgtgg gagccatcg                  169


