                         SEQUENCE LISTING

<110>  OrthoBio
 
<120>  GENE EDITING TO IMPROVE JOINT FUNCTION

<130>  123994-5001-WO

<150>  62/894,184
<151>  2019-08-30

<150>  62/914,635
<151>  2019-10-14

<150>  62/794,340
<151>  2019-01-18

<160>  36    

<170>  PatentIn version 3.5

<210>  1
<211>  271
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Ala Lys Val Pro Asp Met Phe Glu Asp Leu Lys Asn Cys Tyr Ser 
1               5                   10                  15      


Glu Asn Glu Glu Asp Ser Ser Ser Ile Asp His Leu Ser Leu Asn Gln 
            20                  25                  30          


Lys Ser Phe Tyr His Val Ser Tyr Gly Pro Leu His Glu Gly Cys Met 
        35                  40                  45              


Asp Gln Ser Val Ser Leu Ser Ile Ser Glu Thr Ser Lys Thr Ser Lys 
    50                  55                  60                  


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


Leu Lys Lys Arg Arg Leu Ser Leu Ser Gln Ser Ile Thr Asp Asp Asp 
                85                  90                  95      


Leu Glu Ala Ile Ala Asn Asp Ser Glu Glu Glu Ile Ile Lys Pro Arg 
            100                 105                 110         


Ser Ala Pro Phe Ser Phe Leu Ser Asn Val Lys Tyr Asn Phe Met Arg 
        115                 120                 125             


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


Ile Arg Ala Asn Asp Gln Tyr Leu Thr Ala Ala Ala Leu His Asn Leu 
145                 150                 155                 160 


Asp Glu Ala Val Lys Phe Asp Met Gly Ala Tyr Lys Ser Ser Lys Asp 
                165                 170                 175     


Asp Ala Lys Ile Thr Val Ile Leu Arg Ile Ser Lys Thr Gln Leu Tyr 
            180                 185                 190         


Val Thr Ala Gln Asp Glu Asp Gln Pro Val Leu Leu Lys Glu Met Pro 
        195                 200                 205             


Glu Ile Pro Lys Thr Ile Thr Gly Ser Glu Thr Asn Leu Leu Phe Phe 
    210                 215                 220                 


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


Asn Leu Phe Ile Ala Thr Lys Gln Asp Tyr Trp Val Cys Leu Ala Gly 
                245                 250                 255     


Gly Pro Pro Ser Ile Thr Asp Phe Gln Ile Leu Glu Asn Gln Ala 
            260                 265                 270     


<210>  2
<211>  269
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Ala Glu Val Pro Glu Leu Ala Ser Glu Met Met Ala Tyr Tyr Ser 
1               5                   10                  15      


Gly Asn Glu Asp Asp Leu Phe Phe Glu Ala Asp Gly Pro Lys Gln Met 
            20                  25                  30          


Lys Cys Ser Phe Gln Asp Leu Asp Leu Cys Pro Leu Asp Gly Gly Ile 
        35                  40                  45              


Gln Leu Arg Ile Ser Asp His His Tyr Ser Lys Gly Phe Arg Gln Ala 
    50                  55                  60                  


Ala Ser Val Val Val Ala Met Asp Lys Leu Arg Lys Met Leu Val Pro 
65                  70                  75                  80  


Cys Pro Gln Thr Phe Gln Glu Asn Asp Leu Ser Thr Phe Phe Pro Phe 
                85                  90                  95      


Ile Phe Glu Glu Glu Pro Ile Phe Phe Asp Thr Trp Asp Asn Glu Ala 
            100                 105                 110         


Tyr Val His Asp Ala Pro Val Arg Ser Leu Asn Cys Thr Leu Arg Asp 
        115                 120                 125             


Ser Gln Gln Lys Ser Leu Val Met Ser Gly Pro Tyr Glu Leu Lys Ala 
    130                 135                 140                 


Leu His Leu Gln Gly Gln Asp Met Glu Gln Gln Val Val Phe Ser Met 
145                 150                 155                 160 


Ser Phe Val Gln Gly Glu Glu Ser Asn Asp Lys Ile Pro Val Ala Leu 
                165                 170                 175     


Gly Leu Lys Glu Lys Asn Leu Tyr Leu Ser Cys Val Leu Lys Asp Asp 
            180                 185                 190         


Lys Pro Thr Leu Gln Leu Glu Ser Val Asp Pro Lys Asn Tyr Pro Lys 
        195                 200                 205             


Lys Lys Met Glu Lys Arg Phe Val Phe Asn Lys Ile Glu Ile Asn Asn 
    210                 215                 220                 


Lys Leu Glu Phe Glu Ser Ala Gln Phe Pro Asn Trp Tyr Ile Ser Thr 
225                 230                 235                 240 


Ser Gln Ala Glu Asn Met Pro Val Phe Leu Gly Gly Thr Lys Gly Gly 
                245                 250                 255     


Gln Asp Ile Thr Asp Phe Thr Met Gln Phe Val Ser Ser 
            260                 265                 


<210>  3
<211>  270
<212>  PRT
<213>  Mus musculus

<400>  3

Met Ala Lys Val Pro Asp Leu Phe Glu Asp Leu Lys Asn Cys Tyr Ser 
1               5                   10                  15      


Glu Asn Glu Asp Tyr Ser Ser Ala Ile Asp His Leu Ser Leu Asn Gln 
            20                  25                  30          


Lys Ser Phe Tyr Asp Ala Ser Tyr Gly Ser Leu His Glu Thr Cys Thr 
        35                  40                  45              


Asp Gln Phe Val Ser Leu Arg Thr Ser Glu Thr Ser Lys Met Ser Asn 
    50                  55                  60                  


Phe Thr Phe Lys Glu Ser Arg Val Thr Val Ser Ala Thr Ser Ser Asn 
65                  70                  75                  80  


Gly Lys Ile Leu Lys Lys Arg Arg Leu Ser Phe Ser Glu Thr Phe Thr 
                85                  90                  95      


Glu Asp Asp Leu Gln Ser Ile Thr His Asp Leu Glu Glu Thr Ile Gln 
            100                 105                 110         


Pro Arg Ser Ala Pro Tyr Thr Tyr Gln Ser Asp Leu Arg Tyr Lys Leu 
        115                 120                 125             


Met Lys Leu Val Arg Gln Lys Phe Val Met Asn Asp Ser Leu Asn Gln 
    130                 135                 140                 


Thr Ile Tyr Gln Asp Val Asp Lys His Tyr Leu Ser Thr Thr Trp Leu 
145                 150                 155                 160 


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


Gly Gly Asp Asp Ser Lys Tyr Pro Val Thr Leu Lys Ile Ser Asp Ser 
            180                 185                 190         


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


Glu Leu Pro Glu Thr Pro Lys Leu Ile Thr Gly Ser Glu Thr Asp Leu 
    210                 215                 220                 


Ile Phe Phe Trp Lys Ser Ile Asn Ser Lys Asn Tyr Phe Thr Ser Ala 
225                 230                 235                 240 


Ala Tyr Pro Glu Leu Phe Ile Ala Thr Lys Glu Gln Ser Arg Val His 
                245                 250                 255     


Leu Ala Arg Gly Leu Pro Ser Met Thr Asp Phe Gln Ile Ser 
            260                 265                 270 


<210>  4
<211>  269
<212>  PRT
<213>  Mus musculus

<400>  4

Met Ala Thr Val Pro Glu Leu Asn Cys Glu Met Pro Pro Phe Asp Ser 
1               5                   10                  15      


Asp Glu Asn Asp Leu Phe Phe Glu Val Asp Gly Pro Gln Lys Met Lys 
            20                  25                  30          


Gly Cys Phe Gln Thr Phe Asp Leu Gly Cys Pro Asp Glu Ser Ile Gln 
        35                  40                  45              


Leu Gln Ile Ser Gln Gln His Ile Asn Lys Ser Phe Arg Gln Ala Val 
    50                  55                  60                  


Ser Leu Ile Val Ala Val Glu Lys Leu Trp Gln Leu Pro Val Ser Phe 
65                  70                  75                  80  


Pro Trp Thr Phe Gln Asp Glu Asp Met Ser Thr Phe Phe Ser Phe Ile 
                85                  90                  95      


Phe Glu Glu Glu Pro Ile Leu Cys Asp Ser Trp Asp Asp Asp Asp Asn 
            100                 105                 110         


Leu Leu Val Cys Asp Val Pro Ile Arg Gln Leu His Tyr Arg Leu Arg 
        115                 120                 125             


Asp Glu Gln Gln Lys Ser Leu Val Leu Ser Asp Pro Tyr Glu Leu Lys 
    130                 135                 140                 


Ala Leu His Leu Asn Gly Gln Asn Ile Asn Gln Gln Val Ile Phe Ser 
145                 150                 155                 160 


Met Ser Phe Val Gln Gly Glu Pro Ser Asn Asp Lys Ile Pro Val Ala 
                165                 170                 175     


Leu Gly Leu Lys Gly Lys Asn Leu Tyr Leu Ser Cys Val Met Lys Asp 
            180                 185                 190         


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


Lys Lys Lys Met Glu Lys Arg Phe Val Phe Asn Lys Ile Glu Val Lys 
    210                 215                 220                 


Ser Lys Val Glu Phe Glu Ser Ala Glu Phe Pro Asn Trp Tyr Ile Ser 
225                 230                 235                 240 


Thr Ser Gln Ala Glu His Lys Pro Val Phe Leu Gly Asn Asn Ser Gly 
                245                 250                 255     


Gln Asp Ile Ile Asp Phe Thr Met Glu Ser Val Ser Ser 
            260                 265                 


<210>  5
<211>  177
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Glu Ile Cys Arg Gly Leu Arg Ser His Leu Ile Thr Leu Leu Leu 
1               5                   10                  15      


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


Ser Lys Met Gln Ala Phe Arg Ile Trp Asp Val Asn Gln Lys Thr Phe 
        35                  40                  45              


Tyr Leu Arg Asn Asn Gln Leu Val Ala Gly Tyr Leu Gln Gly Pro Asn 
    50                  55                  60                  


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


Leu Phe Leu Gly Ile His Gly Gly Lys Met Cys Leu Ser Cys Val Lys 
                85                  90                  95      


Ser Gly Asp Glu Thr Arg Leu Gln Leu Glu Ala Val Asn Ile Thr Asp 
            100                 105                 110         


Leu Ser Glu Asn Arg Lys Gln Asp Lys Arg Phe Ala Phe Ile Arg Ser 
        115                 120                 125             


Asp Ser Gly Pro Thr Thr Ser Phe Glu Ser Ala Ala Cys Pro Gly Trp 
    130                 135                 140                 


Phe Leu Cys Thr Ala Met Glu Ala Asp Gln Pro Val Ser Leu Thr Asn 
145                 150                 155                 160 


Met Pro Asp Glu Gly Val Met Val Thr Lys Phe Tyr Phe Gln Glu Asp 
                165                 170                 175     


Glu 
    


<210>  6
<211>  178
<212>  PRT
<213>  Mus musculus

<400>  6

Met Glu Ile Cys Trp Gly Pro Tyr Ser His Leu Ile Ser Leu Leu Leu 
1               5                   10                  15      


Ile Leu Leu Phe His Ser Glu Ala Ala Cys Arg Pro Ser Gly Lys Arg 
            20                  25                  30          


Pro Cys Lys Met Gln Ala Phe Arg Ile Trp Asp Thr Asn Gln Lys Thr 
        35                  40                  45              


Phe Tyr Leu Arg Asn Asn Gln Leu Ile Ala Gly Tyr Leu Gln Gly Pro 
    50                  55                  60                  


Asn Ile Lys Leu Glu Glu Lys Ile Asp Met Val Pro Ile Asp Leu His 
65                  70                  75                  80  


Ser Val Phe Leu Gly Ile His Gly Gly Lys Leu Cys Leu Ser Cys Ala 
                85                  90                  95      


Lys Ser Gly Asp Asp Ile Lys Leu Gln Leu Glu Glu Val Asn Ile Thr 
            100                 105                 110         


Asp Leu Ser Lys Asn Lys Glu Glu Asp Lys Arg Phe Thr Phe Ile Arg 
        115                 120                 125             


Ser Glu Lys Gly Pro Thr Thr Ser Phe Glu Ser Ala Ala Cys Pro Gly 
    130                 135                 140                 


Trp Phe Leu Cys Thr Thr Leu Glu Ala Asp Arg Pro Val Ser Leu Thr 
145                 150                 155                 160 


Asn Thr Pro Glu Glu Pro Leu Ile Val Thr Lys Phe Tyr Phe Gln Glu 
                165                 170                 175     


Asp Gln 
        


<210>  7
<211>  20
<212>  DNA
<213>  Mus musculus

<400>  7
gtatcagcaa cgtcaagcaa                                                   20


<210>  8
<211>  20
<212>  DNA
<213>  Mus musculus

<400>  8
ctgcaggtca tcttcagtga                                                   20


<210>  9
<211>  20
<212>  DNA
<213>  Mus musculus

<400>  9
tatcagcaac gtcaagcaac                                                   20


<210>  10
<211>  20
<212>  DNA
<213>  Mus musculus

<400>  10
gccatagctt gcatcataga                                                   20


<210>  11
<211>  20
<212>  DNA
<213>  Mus musculus

<400>  11
catcaacaag agcttcaggc                                                   20


<210>  12
<211>  20
<212>  DNA
<213>  Mus musculus

<400>  12
tgctctcatc aggacagccc                                                   20


<210>  13
<211>  20
<212>  DNA
<213>  Mus musculus

<400>  13
gctcatgtcc tcatcctgga                                                   20


<210>  14
<211>  20
<212>  DNA
<213>  Mus musculus

<400>  14
cctcatcctg gaaggtccac                                                   20


<210>  15
<211>  21
<212>  DNA
<213>  Mus musculus

<400>  15
ttactcctta ccttccagat c                                                 21


<210>  16
<211>  21
<212>  DNA
<213>  Mus musculus

<400>  16
gaaactcagc cgtctcttct t                                                 21


<210>  17
<211>  21
<212>  DNA
<213>  Mus musculus

<400>  17
caacttcacc ttcaaggaga g                                                 21


<210>  18
<211>  21
<212>  DNA
<213>  Mus musculus

<400>  18
gtgtctttcc cgtggacctt c                                                 21


<210>  19
<211>  21
<212>  DNA
<213>  Mus musculus

<400>  19
cacagcttct ccacagccac a                                                 21


<210>  20
<211>  21
<212>  DNA
<213>  Mus musculus

<400>  20
gtgctgctgc gagatttgaa g                                                 21


<210>  21
<211>  20
<212>  RNA
<213>  Mus musculus

<400>  21
guaucagcaa cgucaagcaa                                                   20


<210>  22
<211>  20
<212>  RNA
<213>  Mus musculus

<400>  22
cugcagguca ucuucaguga                                                   20


<210>  23
<211>  20
<212>  RNA
<213>  Mus musculus

<400>  23
uaucagcaac gucaagcaac                                                   20


<210>  24
<211>  20
<212>  RNA
<213>  Mus musculus

<400>  24
gccauagcuu gcaucauaga                                                   20


<210>  25
<211>  20
<212>  RNA
<213>  Mus musculus

<400>  25
caucaacaag agcuucaggc                                                   20


<210>  26
<211>  20
<212>  RNA
<213>  Mus musculus

<400>  26
ugcucucauc aggacagccc                                                   20


<210>  27
<211>  20
<212>  RNA
<213>  Mus musculus

<400>  27
gcucaugucc ucauccugga                                                   20


<210>  28
<211>  20
<212>  RNA
<213>  Mus musculus

<400>  28
ccucauccug gaagguccac                                                   20


<210>  29
<211>  21
<212>  RNA
<213>  Mus musculus

<400>  29
uuacuccuua ccuuccagau c                                                 21


<210>  30
<211>  21
<212>  RNA
<213>  Mus musculus

<400>  30
gaaacucagc cgucucuucu u                                                 21


<210>  31
<211>  21
<212>  RNA
<213>  Mus musculus

<400>  31
caacuucacc uucaaggaga g                                                 21


<210>  32
<211>  21
<212>  RNA
<213>  Mus musculus

<400>  32
gugucuuucc cguggaccuu c                                                 21


<210>  33
<211>  21
<212>  RNA
<213>  Mus musculus

<400>  33
cacagcuucu ccacagccac a                                                 21


<210>  34
<211>  21
<212>  RNA
<213>  Mus musculus

<400>  34
gugcugcugc gagauuugaa g                                                 21


<210>  35
<211>  81
<212>  RNA
<213>  Mus musculus

<400>  35
guuauaguac ucuggaaaca gaaucuacua aaacaaggca aaaugccgug uuuaucucgu       60

caacuuguug gcgagauuuu u                                                 81


<210>  36
<211>  82
<212>  RNA
<213>  Mus musculus

<400>  36
guuauagagc uagaaauagc aaguuaaaau aaggcuaguc cguuaucaac uugaaaaagu       60

ggcaccgagu cggugcuuuu uu                                                82


