                         SEQUENCE LISTING

<110>  Denali Therapeutics Inc.
       Dennis, Mark S.
       Silverman, Adam P.
       Zuchero, Joy Yu
 
<120>  TRANSFERRIN RECEPTOR TRANSGENIC MODELS

<130>  1076191

<150>  US 62/460,692
<151>  2017-02-17

<150>  US 62/543,559
<151>  2017-08-10

<150>  US 62/543,658
<151>  2017-08-10

<150>  US 62/583,314
<151>  2017-11-08

<160>  11    

<170>  PatentIn version 3.5

<210>  1
<211>  184
<212>  PRT
<213>  Homo sapiens

<400>  1

Ala Gln Asn Ser Val Ile Ile Val Asp Lys Asn Gly Arg Leu Val Tyr 
1               5                   10                  15      


Leu Val Glu Asn Pro Gly Gly Tyr Val Ala Tyr Ser Lys Ala Ala Thr 
            20                  25                  30          


Val Thr Gly Lys Leu Val His Ala Asn Phe Gly Thr Lys Lys Asp Phe 
        35                  40                  45              


Glu Asp Leu Tyr Thr Pro Val Asn Gly Ser Ile Val Ile Val Arg Ala 
    50                  55                  60                  


Gly Lys Ile Thr Phe Ala Glu Lys Val Ala Asn Ala Glu Ser Leu Asn 
65                  70                  75                  80  


Ala Ile Gly Val Leu Ile Tyr Met Asp Gln Thr Lys Phe Pro Ile Val 
                85                  90                  95      


Asn Ala Glu Leu Ser Phe Phe Gly His Ala His Leu Gly Thr Gly Asp 
            100                 105                 110         


Pro Tyr Thr Pro Gly Phe Pro Ser Phe Asn His Thr Gln Phe Pro Pro 
        115                 120                 125             


Ser Arg Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr Ile Ser Arg 
    130                 135                 140                 


Ala Ala Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp Cys Pro Ser 
145                 150                 155                 160 


Asp Trp Lys Thr Asp Ser Thr Cys Arg Met Val Thr Ser Glu Ser Lys 
                165                 170                 175     


Asn Val Lys Leu Thr Val Ser Asn 
            180                 


<210>  2
<211>  552
<212>  DNA
<213>  Homo sapiens

<400>  2
gctcagaact ccgtgatcat cgtggataag aacggccggc tggtgtacct ggtggagaac       60

cctggcggat acgtggctta ctctaaggcc gctaccgtga caggcaagct ggtgcacgcc      120

aacttcggaa ccaagaagga ctttgaggat ctgtacacac cagtgaacgg ctctatcgtg      180

atcgtgcgcg ctggaaagat caccttcgcc gagaaggtgg ctaacgccga gagcctgaac      240

gccatcggcg tgctgatcta catggatcag acaaagtttc ccatcgtgaa cgctgagctg      300

tctttctttg gacacgctca cctgggcacc ggagacccat acacacccgg attccctagc      360

tttaaccaca cccagttccc cccttccagg tctagcggac tgccaaacat ccccgtgcag      420

acaatcagca gagccgctgc cgagaagctg tttggcaaca tggagggaga ctgcccctcc      480

gattggaaga ccgactctac atgtaggatg gtgacctccg agtcaaaaaa tgtcaaactc      540

accgtgtcca at                                                          552


<210>  3
<211>  763
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic chimeric transferrin receptor (TfR) polypeptide 
       sequence


<220>
<221>  DOMAIN
<222>  (1)..(67)
<223>  Cytoplasmic Domain

<220>
<221>  DOMAIN
<222>  (68)..(88)
<223>  Transmembrane Domain

<220>
<221>  DOMAIN
<222>  (89)..(763)
<223>  Extracellular Domain

<220>
<221>  DOMAIN
<222>  (198)..(381)
<223>  Apical Domain

<400>  3

Met Met Asp Gln Ala Arg Ser Ala Phe Ser Asn Leu Phe Gly Gly Glu 
1               5                   10                  15      


Pro Leu Ser Tyr Thr Arg Phe Ser Leu Ala Arg Gln Val Asp Gly Asp 
            20                  25                  30          


Asn Ser His Val Glu Met Lys Leu Ala Ala Asp Glu Glu Glu Asn Ala 
        35                  40                  45              


Asp Asn Asn Met Lys Ala Ser Val Arg Lys Pro Lys Arg Phe Asn Gly 
    50                  55                  60                  


Arg Leu Cys Phe Ala Ala Ile Ala Leu Val Ile Phe Phe Leu Ile Gly 
65                  70                  75                  80  


Phe Met Ser Gly Tyr Leu Gly Tyr Cys Lys Arg Val Glu Gln Lys Glu 
                85                  90                  95      


Glu Cys Val Lys Leu Ala Glu Thr Glu Glu Thr Asp Lys Ser Glu Thr 
            100                 105                 110         


Met Glu Thr Glu Asp Val Pro Thr Ser Ser Arg Leu Tyr Trp Ala Asp 
        115                 120                 125             


Leu Lys Thr Leu Leu Ser Glu Lys Leu Asn Ser Ile Glu Phe Ala Asp 
    130                 135                 140                 


Thr Ile Lys Gln Leu Ser Gln Asn Thr Tyr Thr Pro Arg Glu Ala Gly 
145                 150                 155                 160 


Ser Gln Lys Asp Glu Ser Leu Ala Tyr Tyr Ile Glu Asn Gln Phe His 
                165                 170                 175     


Glu Phe Lys Phe Ser Lys Val Trp Arg Asp Glu His Tyr Val Lys Ile 
            180                 185                 190         


Gln Val Lys Ser Ser Ala Gln Asn Ser Val Ile Ile Val Asp Lys Asn 
        195                 200                 205             


Gly Arg Leu Val Tyr Leu Val Glu Asn Pro Gly Gly Tyr Val Ala Tyr 
    210                 215                 220                 


Ser Lys Ala Ala Thr Val Thr Gly Lys Leu Val His Ala Asn Phe Gly 
225                 230                 235                 240 


Thr Lys Lys Asp Phe Glu Asp Leu Tyr Thr Pro Val Asn Gly Ser Ile 
                245                 250                 255     


Val Ile Val Arg Ala Gly Lys Ile Thr Phe Ala Glu Lys Val Ala Asn 
            260                 265                 270         


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


Lys Phe Pro Ile Val Asn Ala Glu Leu Ser Phe Phe Gly His Ala His 
    290                 295                 300                 


Leu Gly Thr Gly Asp Pro Tyr Thr Pro Gly Phe Pro Ser Phe Asn His 
305                 310                 315                 320 


Thr Gln Phe Pro Pro Ser Arg Ser Ser Gly Leu Pro Asn Ile Pro Val 
                325                 330                 335     


Gln Thr Ile Ser Arg Ala Ala Ala Glu Lys Leu Phe Gly Asn Met Glu 
            340                 345                 350         


Gly Asp Cys Pro Ser Asp Trp Lys Thr Asp Ser Thr Cys Arg Met Val 
        355                 360                 365             


Thr Ser Glu Ser Lys Asn Val Lys Leu Thr Val Ser Asn Val Leu Lys 
    370                 375                 380                 


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


Pro Asp Arg Tyr Val Val Val Gly Ala Gln Arg Asp Ala Leu Gly Ala 
                405                 410                 415     


Gly Val Ala Ala Lys Ser Ser Val Gly Thr Gly Leu Leu Leu Lys Leu 
            420                 425                 430         


Ala Gln Val Phe Ser Asp Met Ile Ser Lys Asp Gly Phe Arg Pro Ser 
        435                 440                 445             


Arg Ser Ile Ile Phe Ala Ser Trp Thr Ala Gly Asp Phe Gly Ala Val 
    450                 455                 460                 


Gly Ala Thr Glu Trp Leu Glu Gly Tyr Leu Ser Ser Leu His Leu Lys 
465                 470                 475                 480 


Ala Phe Thr Tyr Ile Asn Leu Asp Lys Val Val Leu Gly Thr Ser Asn 
                485                 490                 495     


Phe Lys Val Ser Ala Ser Pro Leu Leu Tyr Thr Leu Met Gly Lys Ile 
            500                 505                 510         


Met Gln Asp Val Lys His Pro Val Asp Gly Lys Ser Leu Tyr Arg Asp 
        515                 520                 525             


Ser Asn Trp Ile Ser Lys Val Glu Lys Leu Ser Phe Asp Asn Ala Ala 
    530                 535                 540                 


Tyr Pro Phe Leu Ala Tyr Ser Gly Ile Pro Ala Val Ser Phe Cys Phe 
545                 550                 555                 560 


Cys Glu Asp Ala Asp Tyr Pro Tyr Leu Gly Thr Arg Leu Asp Thr Tyr 
                565                 570                 575     


Glu Ala Leu Thr Gln Lys Val Pro Gln Leu Asn Gln Met Val Arg Thr 
            580                 585                 590         


Ala Ala Glu Val Ala Gly Gln Leu Ile Ile Lys Leu Thr His Asp Val 
        595                 600                 605             


Glu Leu Asn Leu Asp Tyr Glu Met Tyr Asn Ser Lys Leu Leu Ser Phe 
    610                 615                 620                 


Met Lys Asp Leu Asn Gln Phe Lys Thr Asp Ile Arg Asp Met Gly Leu 
625                 630                 635                 640 


Ser Leu Gln Trp Leu Tyr Ser Ala Arg Gly Asp Tyr Phe Arg Ala Thr 
                645                 650                 655     


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


Val Met Arg Glu Ile Asn Asp Arg Ile Met Lys Val Glu Tyr His Phe 
        675                 680                 685             


Leu Ser Pro Tyr Val Ser Pro Arg Glu Ser Pro Phe Arg His Ile Phe 
    690                 695                 700                 


Trp Gly Ser Gly Ser His Thr Leu Ser Ala Leu Val Glu Asn Leu Lys 
705                 710                 715                 720 


Leu Arg Gln Lys Asn Ile Thr Ala Phe Asn Glu Thr Leu Phe Arg Asn 
                725                 730                 735     


Gln Leu Ala Leu Ala Thr Trp Thr Ile Gln Gly Val Ala Asn Ala Leu 
            740                 745                 750         


Ser Gly Asp Ile Trp Asn Ile Asp Asn Glu Phe 
        755                 760             


<210>  4
<211>  2329
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  synthetic donor DNA sequence


<220>
<221>  misc_feature
<222>  (1)..(817)
<223>  left homology arm

<220>
<221>  misc_feature
<222>  (821)..(1522)
<223>  codon-optimized sequence

<220>
<221>  misc_feature
<222>  (941)..(1492)
<223>  human apical domain

<220>
<221>  misc_feature
<222>  (1523)..(2329)
<223>  righ homology arm

<400>  4
ctatacagat atataaggat ggggcttttt ttttttaatt tttaaaaaag atttgtttat       60

tattatatgt aagtacactg tagctgtctt cagacactcc agaagagggc atcagatctc      120

attacagatg gttgtgagct accatgtggt cactgggatt tgaactcagg accttcagaa      180

gagcagtcag tgctcttaac tgataagtta ataataagtt aactgataag gtaataaagg      240

tcccctatga aaagggttca gacccaaaga gtcagagatc cacaggttga gaacctcctg      300

ccctaaatct tgttgctctc cttattcaag accactcctg ttgcagttgc tcttaagcat      360

gagtatgctc ccttctgaaa gtctccatag cagccatctc tccagcccca gagtgaggct      420

tttaaaggaa tcttcatgat aaatagaatt tttaaaaaag taactgaagt tacttaaggt      480

gttaaggtac attttattcc ctcagtaact ggttaatcta gcagttttga gtcatacttc      540

atttatcttg actttgaaga gtaagatatt aaaacaattt gcttgatcct tgaagtaagt      600

atttaaatag acattttaat gcagactttt tttagttgac tggtggtgtt gcacgtggtc      660

aatccaagta ctcatgggag gcagaggcag gaggatctct ctctagacca gcctggtcta      720

tagagcaagt tccaggacag ccagggctac acagaaacct tgtttcaaac aagactttta      780

tccttccagg cagctgagcc agaatacata cactcctagg gaagctggtt cacagaagga      840

cgaatccctg gcatactaca tcgagaatca gtttcacgag ttcaagttta gcaaagtctg      900

gagagatgag cactacgtga agatccaggt gaagagctcc gctcagaact ccgtgatcat      960

cgtggataag aacggccggc tggtgtacct ggtggagaac cctggcggat acgtggctta     1020

ctctaaggcc gctaccgtga caggcaagct ggtgcacgcc aacttcggaa ccaagaagga     1080

ctttgaggat ctgtacacac cagtgaacgg ctctatcgtg atcgtgcgcg ctggaaagat     1140

caccttcgcc gagaaggtgg ctaacgccga gagcctgaac gccatcggcg tgctgatcta     1200

catggatcag acaaagtttc ccatcgtgaa cgctgagctg tctttctttg gacacgctca     1260

cctgggcacc ggagacccat acacacccgg attccctagc tttaaccaca cccagttccc     1320

cccttccagg tctagcggac tgccaaacat ccccgtgcag acaatcagca gagccgctgc     1380

cgagaagctg tttggcaaca tggagggaga ctgcccctcc gattggaaga ccgactctac     1440

atgtaggatg gtgacctccg agtcaaaaaa tgtcaaactc accgtgtcca atgtgctgaa     1500

agaacgacgc atcctgaata tctttggagt tattaaaggt tatgaggaac caggtaaaga     1560

cctgctttgt actttttcac tttactgttt tgcttactgt agataggtct agtgcaggaa     1620

ggagaaggat gctagcttgg catgaactgc tatatcttgt ttgtcctaat gtgaactttg     1680

taatatatgt gtatataaca cataatatgg ccatgtaagt gtatggagag gccagagtta     1740

agtattaaat atctttctgt aatcatttaa aattttacat atgaaggtca gtgaacagat     1800

tgaaggagtt ttgtccaggt gggacttgga tctaaatttt ttacaatgcc tggcagcaaa     1860

caccttttta atcaactgag ctgtctcccc aaataaagtg aatgtgatat cagcttgtgg     1920

ataatttttt tttgttgctt tgataagtgg ttttcttaca ggatcacata ccagttctgt     1980

ccatagcatt aaacaaacat aactgtcatg cagtagatta atgtgcaggg cacatccaac     2040

agtcacattt attaatagga caaaaagttg gaccttatat gtagcacacc tataattcca     2100

gtgctaggaa gatccgggta ggagatcctt agttcggtgc tacttagtga gggtttgttt     2160

caaaaaacaa aagctatgat ggtgtgttgc cttttttctt ttagaccgtt atgttgtagt     2220

aggagcccag agagacgctt tgggtgctgg tgttgcggcg aagtccagtg tgggaacagg     2280

tcttctgttg aaacttgccc aagtattctc agatatgatt tcaaaaggt                 2329


<210>  5
<211>  763
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(67)
<223>  cytoplasmic domain

<220>
<221>  DOMAIN
<222>  (68)..(88)
<223>  transmembrane domain

<220>
<221>  DOMAIN
<222>  (89)..(763)
<223>  extracellular domain

<220>
<221>  DOMAIN
<222>  (199)..(381)
<223>  apical domain

<400>  5

Met Met Asp Gln Ala Arg Ser Ala Phe Ser Asn Leu Phe Gly Gly Glu 
1               5                   10                  15      


Pro Leu Ser Tyr Thr Arg Phe Ser Leu Ala Arg Gln Val Asp Gly Asp 
            20                  25                  30          


Asn Ser His Val Glu Met Lys Leu Ala Ala Asp Glu Glu Glu Asn Ala 
        35                  40                  45              


Asp Asn Asn Met Lys Ala Ser Val Arg Lys Pro Lys Arg Phe Asn Gly 
    50                  55                  60                  


Arg Leu Cys Phe Ala Ala Ile Ala Leu Val Ile Phe Phe Leu Ile Gly 
65                  70                  75                  80  


Phe Met Ser Gly Tyr Leu Gly Tyr Cys Lys Arg Val Glu Gln Lys Glu 
                85                  90                  95      


Glu Cys Val Lys Leu Ala Glu Thr Glu Glu Thr Asp Lys Ser Glu Thr 
            100                 105                 110         


Met Glu Thr Glu Asp Val Pro Thr Ser Ser Arg Leu Tyr Trp Ala Asp 
        115                 120                 125             


Leu Lys Thr Leu Leu Ser Glu Lys Leu Asn Ser Ile Glu Phe Ala Asp 
    130                 135                 140                 


Thr Ile Lys Gln Leu Ser Gln Asn Thr Tyr Thr Pro Arg Glu Ala Gly 
145                 150                 155                 160 


Ser Gln Lys Asp Glu Ser Leu Ala Tyr Tyr Ile Glu Asn Gln Phe His 
                165                 170                 175     


Glu Phe Lys Phe Ser Lys Val Trp Arg Asp Glu His Tyr Val Lys Ile 
            180                 185                 190         


Gln Val Lys Ser Ser Ile Gly Gln Asn Met Val Thr Ile Val Gln Ser 
        195                 200                 205             


Asn Gly Asn Leu Asp Pro Val Glu Ser Pro Glu Gly Tyr Val Ala Phe 
    210                 215                 220                 


Ser Lys Pro Thr Glu Val Ser Gly Lys Leu Val His Ala Asn Phe Gly 
225                 230                 235                 240 


Thr Lys Lys Asp Phe Glu Glu Leu Ser Tyr Ser Val Asn Gly Ser Leu 
                245                 250                 255     


Val Ile Val Arg Ala Gly Glu Ile Thr Phe Ala Glu Lys Val Ala Asn 
            260                 265                 270         


Ala Gln Ser Phe Asn Ala Ile Gly Val Leu Ile Tyr Met Asp Lys Asn 
        275                 280                 285             


Lys Phe Pro Val Val Glu Ala Asp Leu Ala Leu Phe Gly His Ala His 
    290                 295                 300                 


Leu Gly Thr Gly Asp Pro Tyr Thr Pro Gly Phe Pro Ser Phe Asn His 
305                 310                 315                 320 


Thr Gln Phe Pro Pro Ser Gln Ser Ser Gly Leu Pro Asn Ile Pro Val 
                325                 330                 335     


Gln Thr Ile Ser Arg Ala Ala Ala Glu Lys Leu Phe Gly Lys Met Glu 
            340                 345                 350         


Gly Ser Cys Pro Ala Arg Trp Asn Ile Asp Ser Ser Cys Lys Leu Glu 
        355                 360                 365             


Leu Ser Gln Asn Gln Asn Val Lys Leu Ile Val Lys Asn Val Leu Lys 
    370                 375                 380                 


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


Pro Asp Arg Tyr Val Val Val Gly Ala Gln Arg Asp Ala Leu Gly Ala 
                405                 410                 415     


Gly Val Ala Ala Lys Ser Ser Val Gly Thr Gly Leu Leu Leu Lys Leu 
            420                 425                 430         


Ala Gln Val Phe Ser Asp Met Ile Ser Lys Asp Gly Phe Arg Pro Ser 
        435                 440                 445             


Arg Ser Ile Ile Phe Ala Ser Trp Thr Ala Gly Asp Phe Gly Ala Val 
    450                 455                 460                 


Gly Ala Thr Glu Trp Leu Glu Gly Tyr Leu Ser Ser Leu His Leu Lys 
465                 470                 475                 480 


Ala Phe Thr Tyr Ile Asn Leu Asp Lys Val Val Leu Gly Thr Ser Asn 
                485                 490                 495     


Phe Lys Val Ser Ala Ser Pro Leu Leu Tyr Thr Leu Met Gly Lys Ile 
            500                 505                 510         


Met Gln Asp Val Lys His Pro Val Asp Gly Lys Ser Leu Tyr Arg Asp 
        515                 520                 525             


Ser Asn Trp Ile Ser Lys Val Glu Lys Leu Ser Phe Asp Asn Ala Ala 
    530                 535                 540                 


Tyr Pro Phe Leu Ala Tyr Ser Gly Ile Pro Ala Val Ser Phe Cys Phe 
545                 550                 555                 560 


Cys Glu Asp Ala Asp Tyr Pro Tyr Leu Gly Thr Arg Leu Asp Thr Tyr 
                565                 570                 575     


Glu Ala Leu Thr Gln Lys Val Pro Gln Leu Asn Gln Met Val Arg Thr 
            580                 585                 590         


Ala Ala Glu Val Ala Gly Gln Leu Ile Ile Lys Leu Thr His Asp Val 
        595                 600                 605             


Glu Leu Asn Leu Asp Tyr Glu Met Tyr Asn Ser Lys Leu Leu Ser Phe 
    610                 615                 620                 


Met Lys Asp Leu Asn Gln Phe Lys Thr Asp Ile Arg Asp Met Gly Leu 
625                 630                 635                 640 


Ser Leu Gln Trp Leu Tyr Ser Ala Arg Gly Asp Tyr Phe Arg Ala Thr 
                645                 650                 655     


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


Val Met Arg Glu Ile Asn Asp Arg Ile Met Lys Val Glu Tyr His Phe 
        675                 680                 685             


Leu Ser Pro Tyr Val Ser Pro Arg Glu Ser Pro Phe Arg His Ile Phe 
    690                 695                 700                 


Trp Gly Ser Gly Ser His Thr Leu Ser Ala Leu Val Glu Asn Leu Lys 
705                 710                 715                 720 


Leu Arg Gln Lys Asn Ile Thr Ala Phe Asn Glu Thr Leu Phe Arg Asn 
                725                 730                 735     


Gln Leu Ala Leu Ala Thr Trp Thr Ile Gln Gly Val Ala Asn Ala Leu 
            740                 745                 750         


Ser Gly Asp Ile Trp Asn Ile Asp Asn Glu Phe 
        755                 760             


<210>  6
<211>  760
<212>  PRT
<213>  Homo sapiens


<220>
<221>  DOMAIN
<222>  (1)..(67)
<223>  cytoplasmic domain

<220>
<221>  DOMAIN
<222>  (68)..(89)
<223>  transmembrane domain

<220>
<221>  DOMAIN
<222>  (90)..(760)
<223>  extracellular domain

<220>
<221>  DOMAIN
<222>  (196)..(379)
<223>  apical domain

<400>  6

Met Met Asp Gln Ala Arg Ser Ala Phe Ser Asn Leu Phe Gly Gly Glu 
1               5                   10                  15      


Pro Leu Ser Tyr Thr Arg Phe Ser Leu Ala Arg Gln Val Asp Gly Asp 
            20                  25                  30          


Asn Ser His Val Glu Met Lys Leu Ala Val Asp Glu Glu Glu Asn Ala 
        35                  40                  45              


Asp Asn Asn Thr Lys Ala Asn Val Thr Lys Pro Lys Arg Cys Ser Gly 
    50                  55                  60                  


Ser Ile Cys Tyr Gly Thr Ile Ala Val Ile Val Phe Phe Leu Ile Gly 
65                  70                  75                  80  


Phe Met Ile Gly Tyr Leu Gly Tyr Cys Lys Gly Val Glu Pro Lys Thr 
                85                  90                  95      


Glu Cys Glu Arg Leu Ala Gly Thr Glu Ser Pro Val Arg Glu Glu Pro 
            100                 105                 110         


Gly Glu Asp Phe Pro Ala Ala Arg Arg Leu Tyr Trp Asp Asp Leu Lys 
        115                 120                 125             


Arg Lys Leu Ser Glu Lys Leu Asp Ser Thr Asp Phe Thr Gly Thr Ile 
    130                 135                 140                 


Lys Leu Leu Asn Glu Asn Ser Tyr Val Pro Arg Glu Ala Gly Ser Gln 
145                 150                 155                 160 


Lys Asp Glu Asn Leu Ala Leu Tyr Val Glu Asn Gln Phe Arg Glu Phe 
                165                 170                 175     


Lys Leu Ser Lys Val Trp Arg Asp Gln His Phe Val Lys Ile Gln Val 
            180                 185                 190         


Lys Asp Ser Ala Gln Asn Ser Val Ile Ile Val Asp Lys Asn Gly Arg 
        195                 200                 205             


Leu Val Tyr Leu Val Glu Asn Pro Gly Gly Tyr Val Ala Tyr Ser Lys 
    210                 215                 220                 


Ala Ala Thr Val Thr Gly Lys Leu Val His Ala Asn Phe Gly Thr Lys 
225                 230                 235                 240 


Lys Asp Phe Glu Asp Leu Tyr Thr Pro Val Asn Gly Ser Ile Val Ile 
                245                 250                 255     


Val Arg Ala Gly Lys Ile Thr Phe Ala Glu Lys Val Ala Asn Ala Glu 
            260                 265                 270         


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


Pro Ile Val Asn Ala Glu Leu Ser Phe Phe Gly His Ala His Leu Gly 
    290                 295                 300                 


Thr Gly Asp Pro Tyr Thr Pro Gly Phe Pro Ser Phe Asn His Thr Gln 
305                 310                 315                 320 


Phe Pro Pro Ser Arg Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr 
                325                 330                 335     


Ile Ser Arg Ala Ala Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp 
            340                 345                 350         


Cys Pro Ser Asp Trp Lys Thr Asp Ser Thr Cys Arg Met Val Thr Ser 
        355                 360                 365             


Glu Ser Lys Asn Val Lys Leu Thr Val Ser Asn Val Leu Lys Glu Ile 
    370                 375                 380                 


Lys Ile Leu Asn Ile Phe Gly Val Ile Lys Gly Phe Val Glu Pro Asp 
385                 390                 395                 400 


His Tyr Val Val Val Gly Ala Gln Arg Asp Ala Trp Gly Pro Gly Ala 
                405                 410                 415     


Ala Lys Ser Gly Val Gly Thr Ala Leu Leu Leu Lys Leu Ala Gln Met 
            420                 425                 430         


Phe Ser Asp Met Val Leu Lys Asp Gly Phe Gln Pro Ser Arg Ser Ile 
        435                 440                 445             


Ile Phe Ala Ser Trp Ser Ala Gly Asp Phe Gly Ser Val Gly Ala Thr 
    450                 455                 460                 


Glu Trp Leu Glu Gly Tyr Leu Ser Ser Leu His Leu Lys Ala Phe Thr 
465                 470                 475                 480 


Tyr Ile Asn Leu Asp Lys Ala Val Leu Gly Thr Ser Asn Phe Lys Val 
                485                 490                 495     


Ser Ala Ser Pro Leu Leu Tyr Thr Leu Ile Glu Lys Thr Met Gln Asn 
            500                 505                 510         


Val Lys His Pro Val Thr Gly Gln Phe Leu Tyr Gln Asp Ser Asn Trp 
        515                 520                 525             


Ala Ser Lys Val Glu Lys Leu Thr Leu Asp Asn Ala Ala Phe Pro Phe 
    530                 535                 540                 


Leu Ala Tyr Ser Gly Ile Pro Ala Val Ser Phe Cys Phe Cys Glu Asp 
545                 550                 555                 560 


Thr Asp Tyr Pro Tyr Leu Gly Thr Thr Met Asp Thr Tyr Lys Glu Leu 
                565                 570                 575     


Ile Glu Arg Ile Pro Glu Leu Asn Lys Val Ala Arg Ala Ala Ala Glu 
            580                 585                 590         


Val Ala Gly Gln Phe Val Ile Lys Leu Thr His Asp Val Glu Leu Asn 
        595                 600                 605             


Leu Asp Tyr Glu Arg Tyr Asn Ser Gln Leu Leu Ser Phe Val Arg Asp 
    610                 615                 620                 


Leu Asn Gln Tyr Arg Ala Asp Ile Lys Glu Met Gly Leu Ser Leu Gln 
625                 630                 635                 640 


Trp Leu Tyr Ser Ala Arg Gly Asp Phe Phe Arg Ala Thr Ser Arg Leu 
                645                 650                 655     


Thr Thr Asp Phe Gly Asn Ala Glu Lys Thr Asp Arg Phe Val Met Lys 
            660                 665                 670         


Lys Leu Asn Asp Arg Val Met Arg Val Glu Tyr His Phe Leu Ser Pro 
        675                 680                 685             


Tyr Val Ser Pro Lys Glu Ser Pro Phe Arg His Val Phe Trp Gly Ser 
    690                 695                 700                 


Gly Ser His Thr Leu Pro Ala Leu Leu Glu Asn Leu Lys Leu Arg Lys 
705                 710                 715                 720 


Gln Asn Asn Gly Ala Phe Asn Glu Thr Leu Phe Arg Asn Gln Leu Ala 
                725                 730                 735     


Leu Ala Thr Trp Thr Ile Gln Gly Ala Ala Asn Ala Leu Ser Gly Asp 
            740                 745                 750         


Val Trp Asp Ile Asp Asn Glu Phe 
        755                 760 


<210>  7
<211>  184
<212>  PRT
<213>  Macaca mulatta

<400>  7

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


Leu Val Glu Asn Pro Gly Gly Tyr Val Ala Tyr Ser Lys Ala Ala Thr 
            20                  25                  30          


Val Thr Gly Lys Leu Val His Ala Asn Phe Gly Thr Lys Lys Asp Phe 
        35                  40                  45              


Glu Asp Leu Asp Ser Pro Val Asn Gly Ser Ile Val Ile Val Arg Ala 
    50                  55                  60                  


Gly Lys Ile Thr Phe Ala Glu Lys Val Ala Asn Ala Glu Ser Leu Asn 
65                  70                  75                  80  


Ala Ile Gly Val Leu Ile Tyr Met Asp Gln Thr Lys Phe Pro Ile Val 
                85                  90                  95      


Lys Ala Asp Leu Ser Phe Phe Gly His Ala His Leu Gly Thr Gly Asp 
            100                 105                 110         


Pro Tyr Thr Pro Gly Phe Pro Ser Phe Asn His Thr Gln Phe Pro Pro 
        115                 120                 125             


Ser Gln Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr Ile Ser Arg 
    130                 135                 140                 


Ala Ala Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp Cys Pro Ser 
145                 150                 155                 160 


Asp Trp Lys Thr Asp Ser Thr Cys Lys Met Val Thr Ser Glu Asn Lys 
                165                 170                 175     


Ser Val Lys Leu Thr Val Ser Asn 
            180                 


<210>  8
<211>  184
<212>  PRT
<213>  Pan troglodytes

<400>  8

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


Leu Val Glu Asn Pro Gly Gly Tyr Val Ala Tyr Ser Lys Ala Ala Thr 
            20                  25                  30          


Val Thr Gly Lys Leu Val His Ala Asn Phe Gly Thr Lys Lys Asp Phe 
        35                  40                  45              


Glu Asp Leu His Thr Pro Val Asn Gly Ser Ile Val Ile Val Arg Ala 
    50                  55                  60                  


Gly Lys Ile Thr Phe Ala Glu Lys Val Ala Asn Ala Glu Ser Leu Asn 
65                  70                  75                  80  


Ala Ile Gly Val Leu Ile Tyr Met Asp Gln Thr Lys Phe Pro Ile Val 
                85                  90                  95      


Asn Ala Glu Leu Ser Phe Phe Gly His Ala His Leu Gly Thr Gly Asp 
            100                 105                 110         


Pro Tyr Thr Pro Gly Phe Pro Ser Phe Asn His Thr Gln Phe Pro Pro 
        115                 120                 125             


Ser Arg Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr Val Ser Arg 
    130                 135                 140                 


Ala Ala Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp Cys Pro Ser 
145                 150                 155                 160 


Asp Trp Lys Thr Asp Ser Thr Cys Arg Met Val Thr Ser Glu Ser Lys 
                165                 170                 175     


Asn Val Lys Leu Thr Val Ser Asn 
            180                 


<210>  9
<211>  184
<212>  PRT
<213>  Macaca fascicularis

<400>  9

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


Leu Val Glu Asn Pro Gly Gly Tyr Val Ala Tyr Ser Lys Ala Ala Thr 
            20                  25                  30          


Val Thr Gly Lys Leu Val His Ala Asn Phe Gly Thr Lys Lys Asp Phe 
        35                  40                  45              


Glu Asp Leu Asp Ser Pro Val Asn Gly Ser Ile Val Ile Val Arg Ala 
    50                  55                  60                  


Gly Lys Ile Thr Phe Ala Glu Lys Val Ala Asn Ala Glu Ser Leu Asn 
65                  70                  75                  80  


Ala Ile Gly Val Leu Ile Tyr Met Asp Gln Thr Lys Phe Pro Ile Val 
                85                  90                  95      


Lys Ala Asp Leu Ser Phe Phe Gly His Ala His Leu Gly Thr Gly Asp 
            100                 105                 110         


Pro Tyr Thr Pro Gly Phe Pro Ser Phe Asn His Thr Gln Phe Pro Pro 
        115                 120                 125             


Ser Gln Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr Ile Ser Arg 
    130                 135                 140                 


Ala Ala Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp Cys Pro Ser 
145                 150                 155                 160 


Asp Trp Lys Thr Asp Ser Thr Cys Lys Met Val Thr Ser Glu Asn Lys 
                165                 170                 175     


Ser Val Lys Leu Thr Val Ser Asn 
            180                 


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

<220>
<223>  synthetic sgRNA sequence

<400>  10
gaatacatac actcctcgtg agg                                               23


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

<220>
<223>  synthetic sgRNA sequence

<400>  11
agaagaatac ttaacatctt tgg                                               23


