
                                SEQUENCE LISTING

<110> Regeneron Pharmaceuticals, Inc.

<120> METHODS FOR BREAKING IMMUNOLOGICAL
  TOLERANCE USING MULTIPLE GUIDE RNAS
  

<130> 057766/497023

<150> 62/339,472          
<151> 2016-05-20  

<150> 62/368,604          
<151> 2016-07-29  

<160> 152

<170> FastSEQ for Windows Version 4.0

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

<220> 
<223> Guide RNA recognition sequence

<220> 
<221> misc_feature   
<222> (2)...(21)
<223> n = A, T, C, or G

<400> 1
gnnnnnnnnn nnnnnnnnnn ngg                                         23

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

<220> 
<223> Guide RNA recognition sequence

<220> 
<221> misc_feature   
<222> (1)...(21)
<223> n = A, T, C, or G

<400> 2
nnnnnnnnnn nnnnnnnnnn ngg                                         23

<210> 3
<211> 25
<212> DNA
<213> Artificial Sequence

<220> 
<223> Guide RNA recognition sequence

<220> 
<221> misc_feature   
<222> (3)...(23)
<223> n = A, T, C, or G

<400> 3
ggnnnnnnnn nnnnnnnnnn nnngg                                       25

<210> 4
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> C5 (Hc) gRNA A DNA-targeting segment (100 bp from
      target locus endpoint)

<400> 4
atcacaaacc agttaaccgg                                             20

<210> 5
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> C5 (Hc) gRNA B DNA-targeting segment (500 bp from
      target locus endpoint)

<400> 5
tttcagacga gccgacccgg                                             20

<210> 6
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> C5 (Hc) gRNA C DNA-targeting segment (38200 and
      37500 bp from target locus endpoints)

<400> 6
tgtgtgtcat agcgatgtcg                                             20

<210> 7
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> C5 (Hc) gRNA D DNA-targeting segment (43500 and
      32200 bp from target locus endpoints)

<400> 7
aacaggtacc ctatcctcac                                             20

<210> 8
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> C5 (Hc) gRNA E DNA-targeting segment (500 bp from
      target locus endpoint)

<400> 8
ggcccggacc tagtctctct                                             20

<210> 9
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> C5 (Hc) gRNA E2 DNA-targeting segment (100 bp from
      target locus endpoint)

<400> 9
tcgtggttgc atgcgcactg                                             20

<210> 10
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Lrp5 gRNA A DNA-targeting segment (50 bp from
      target locus end point)

<400> 10
gggaacccac agcatactcc                                             20

<210> 11
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Lrp5 gRNA B DNA-targeting segment (500 bp from
      target locus end point)

<400> 11
gaatcatgca cggctacccc                                             20

<210> 12
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Lrp5 gRNA B2 DNA-targeting segment (1000 bp from
      target locus end point)

<400> 12
tgctcctatg gggaggcgcg                                             20

<210> 13
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Lrp5 gRNA C DNA-targeting segment (29900 and 38430
      bp from target locus end points)

<400> 13
actgagatca atgaccccga                                             20

<210> 14
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Lrp5 gRNA D DNA-targeting segment (29950 and 38380
      bp from target locus end points)

<400> 14
gggtcgcccg gaacctctac                                             20

<210> 15
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Lrp5 gRNA E2 DNA-targeting segment (1000 bp from
      target locus end point)

<400> 15
cttggataac attgataccc                                             20

<210> 16
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Lrp5 gRNA E DNA-targeting segment (500 bp from
      target locus end point)

<400> 16
ggggcagagc ccttatatca                                             20

<210> 17
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Lrp5 gRNA F DNA-targeting segment (50 bp from
      target locus end point)

<400> 17
tcgctcacat taatccctag                                             20

<210> 18
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Ror1 gRNA A DNA-targeting segment (200 bp from
      target locus end point)

<400> 18
tgtgggcctt tgctgatcac                                             20

<210> 19
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Ror1 gRNA B DNA-targeting segment (1000 bp from
      target locus end point)

<400> 19
aatctatgat cctatggcct                                             20

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

<220> 
<223> Ror1 gRNA D DNA-targeting segment (54300 and 55500
      bp from target locus end points)

<400> 20
tgccaatagc agtgacttga                                             20

<210> 21
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Ror1 gRNA C DNA-targeting segment (54500 and 55300
      bp from target locus end points)

<400> 21
gggaagaatg ggctattgtc                                             20

<210> 22
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Ror1 gRNA E DNA-targeting segment (1000 bp from
      target locus end point)

<400> 22
ggttgtttgt gctgatgacg                                             20

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

<220> 
<223> Ror1 gRNA F DNA-targeting segment (200 bp from
      target locus end point)

<400> 23
ccgtcctagg ccttctacgt                                             20

<210> 24
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Trpa1 gRNA A DNA-targeting segment (100 bp from
      target locus end point)

<400> 24
gtactgggga atcggtggtc                                             20

<210> 25
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Trpa1 gRNA A2 DNA-targeting segment (500 bp from
      target locus end point)

<400> 25
cacgcactcc aaatttatcc                                             20

<210> 26
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Trpa1 gRNA B DNA-targeting segment (1000 bp from
      target locus end point)

<400> 26
ctaagtgtgt atcagtacat                                             20

<210> 27
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Trpa1 gRNA C DNA-targeting segment (25600 and
      19740 bp from target locus end points)

<400> 27
tgccctgcac aataagcgca                                             20

<210> 28
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Trpa1 gRNA D DNA-targeting segment (26970 and
      18370 bp from target locus end points)

<400> 28
actcattgaa acgttatggc                                             20

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

<220> 
<223> Trpa1 gRNA E2 DNA-targeting segment (1000 bp from
      target locus end point)

<400> 29
agtaagggtg gattaaattc                                             20

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

<220> 
<223> Trpa1 gRNA E DNA-targeting segment (500 bp from
      target locus end point)

<400> 30
gccatctaga ttcatgtaac                                             20

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

<220> 
<223> Trpa1 gRNA F DNA-targeting segment (100 bp from
      target locus end point)

<400> 31
gactagaaat gttctgcacc                                             20

<210> 32
<211> 21
<212> DNA
<213> Artificial Sequence

<220> 
<223> 190045 forward primer

<400> 32
gagctcatag ccaacagctt g                                           21

<210> 33
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> 190061 forward primer

<400> 33
atgcatcaga tcacgctcag                                             20

<210> 34
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> 190068 forward primer

<400> 34
gtccttgtgg catttccaac                                             20

<210> 35
<211> 24
<212> DNA
<213> Artificial Sequence

<220> 
<223> 190030 forward primer

<400> 35
ccagtatggt gtcagttaat agcg                                        24

<210> 36
<211> 19
<212> DNA
<213> Artificial Sequence

<220> 
<223> 190033 forward primer (same as forward primer for
      SV 48.3 in Fig. 6)

<400> 36
ctgtgcagaa agcagcctc                                              19

<210> 37
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> 190013 forward primer

<400> 37
cctctccctc taggcacctg                                             20

<210> 38
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> 190045 reverse primer

<400> 38
tctttaaggg ctccgttgtc                                             20

<210> 39
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> 190061 reverse primer

<400> 39
aagaccaacc attcacccag                                             20

<210> 40
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> 190068 reverse primer

<400> 40
ttcccagtcc aagtcaaagg                                             20

<210> 41
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> 190030 reverse primer

<400> 41
ctgttatctg caaggcaccc                                             20

<210> 42
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> 190033 reverse primer (same as reverse primer for
      SV 48.3 in Fig. 6)

<400> 42
acaactggat cctgattcgc                                             20

<210> 43
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> 190013 reverse primer

<400> 43
taagagggca tgggtgagac                                             20

<210> 44
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> C2 probe (B6) - SNV 0.32 in Fig. 6

<400> 44
aattcagaag acctatcgta                                             20

<210> 45
<211> 21
<212> DNA
<213> Artificial Sequence

<220> 
<223> T3 probe (B6) - SNV 1.2 in Fig. 6

<400> 45
tatgtgtata ggtgtttgga t                                           21

<210> 46
<211> 19
<212> DNA
<213> Artificial Sequence

<220> 
<223> T6 probe (B6) - SNV 11.1 in Fig. 6

<400> 46
tacattgcta aatgaaacc                                              19

<210> 47
<211> 16
<212> DNA
<213> Artificial Sequence

<220> 
<223> T7 probe (B6) - SNV 13.2 in Fig. 6

<400> 47
cgcagtcatg cacata                                                 16

<210> 48
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> T8 probe (B6) - SNV 17.5 in Fig. 6

<400> 48
ttataaagcc cagtatgtac                                             20

<210> 49
<211> 14
<212> DNA
<213> Artificial Sequence

<220> 
<223> T9 probe (B6) - SNV 25.8 in Fig. 6

<400> 49
tgctgcataa tcag                                                   14

<210> 50
<211> 18
<212> DNA
<213> Artificial Sequence

<220> 
<223> T10 probe (B6) - SNV 33.0 in Fig. 6

<400> 50
tcaggagtga attggata                                               18

<210> 51
<211> 16
<212> DNA
<213> Artificial Sequence

<220> 
<223> T11 probe (B6) - SNV 38.3 in Fig. 6

<400> 51
ctgctactta cctttg                                                 16

<210> 52
<211> 13
<212> DNA
<213> Artificial Sequence

<220> 
<223> T13 probe (B6) - SNV 49.6 in Fig. 6

<400> 52
aggaggaaaa cgc                                                    13

<210> 53
<211> 17
<212> DNA
<213> Artificial Sequence

<220> 
<223> T14 probe (B6) - SNV 57.2 in Fig. 6

<400> 53
cctttgttcc tcataag                                                17

<210> 54
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> C2 probe (129) - SNV 0.32 in Fig. 6

<400> 54
aattcagaag acctattgta                                             20

<210> 55
<211> 21
<212> DNA
<213> Artificial Sequence

<220> 
<223> T3 probe (129) - SNV 1.2 in Fig. 6

<400> 55
tatgtgtata ggtgtttgca t                                           21

<210> 56
<211> 16
<212> DNA
<213> Artificial Sequence

<220> 
<223> T6 probe (129) - SNV 11.1 in Fig. 6

<400> 56
cattgctaca tgaaac                                                 16

<210> 57
<211> 16
<212> DNA
<213> Artificial Sequence

<220> 
<223> T7 probe (129) - SNV 13.2 in Fig. 6

<400> 57
cgcagtcatg cacgta                                                 16

<210> 58
<211> 23
<212> DNA
<213> Artificial Sequence

<220> 
<223> T8 probe (129) - SNV 17.5 in Fig. 6

<400> 58
tgagaattta taaagcccaa tat                                         23

<210> 59
<211> 14
<212> DNA
<213> Artificial Sequence

<220> 
<223> T9 probe (129) - SNV 25.8 in Fig. 6

<400> 59
tgctgcatga tcag                                                   14

<210> 60
<211> 15
<212> DNA
<213> Artificial Sequence

<220> 
<223> T10 probe (129) - SNV 33.0 in Fig. 6

<400> 60
tcaggagtga atcgg                                                  15

<210> 61
<211> 16
<212> DNA
<213> Artificial Sequence

<220> 
<223> T11 probe (129) - SNV 38.3 in Fig. 6

<400> 61
ctgctagtta cctttg                                                 16

<210> 62
<211> 15
<212> DNA
<213> Artificial Sequence

<220> 
<223> T13 probe (129) - SNV 49.6 in Fig. 6

<400> 62
aggaggaaga cgcag                                                  15

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

<220> 
<223> T14 probe (129) - SNV 57.2 in Fig. 6

<400> 63
ctttgttctt cataagc                                                17

<210> 64
<211> 25
<212> DNA
<213> Artificial Sequence

<220> 
<223> C2 forward primer - SNV 0.32 in Fig. 6

<400> 64
atgagggatt tccttaatca gacaa                                       25

<210> 65
<211> 29
<212> DNA
<213> Artificial Sequence

<220> 
<223> T3 forward primer - SNV 1.2 in Fig. 6

<400> 65
tggtatgttt attcttactc aaggttttg                                   29

<210> 66
<211> 22
<212> DNA
<213> Artificial Sequence

<220> 
<223> T6 forward primer - SNV 11.1 in Fig. 6

<400> 66
gggcaactga tggaaagaac tc                                          22

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

<220> 
<223> T7 forward primer - SNV 13.2 in Fig. 6

<400> 67
gactgacgca caaacttgtc ctt                                         23

<210> 68
<211> 26
<212> DNA
<213> Artificial Sequence

<220> 
<223> T8 forward primer - SNV 17.5 in Fig. 6

<400> 68
cccaaagcat ataacaagaa caaatg                                      26

<210> 69
<211> 18
<212> DNA
<213> Artificial Sequence

<220> 
<223> T9 forward primer - SNV 25.8 in Fig. 6

<400> 69
gcaggacgca ggcgttta                                               18

<210> 70
<211> 23
<212> DNA
<213> Artificial Sequence

<220> 
<223> T10 forward primer - SNV 33.0 in Fig. 6

<400> 70
gcatcctcat ggcagtctac atc                                         23

<210> 71
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> T11 forward primer - SNV 38.3 in Fig. 6

<400> 71
cctgcccctt gatgagtgtt                                             20

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

<220> 
<223> T13 forward primer - SNV 49.6 in Fig. 6

<400> 72
ccctctttga tatgctcgtg tgt                                         23

<210> 73
<211> 22
<212> DNA
<213> Artificial Sequence

<220> 
<223> T14 forward primer - SNV 57.2 in Fig. 6

<400> 73
tcccacaggt ccatgtcttt aa                                          22

<210> 74
<211> 28
<212> DNA
<213> Artificial Sequence

<220> 
<223> C2 reverse primer - SNV 0.32 in Fig. 6

<400> 74
agactacaat gagctaccat cataaggt                                    28

<210> 75
<211> 24
<212> DNA
<213> Artificial Sequence

<220> 
<223> T3 reverse primer - SNV 1.2 in Fig. 6

<400> 75
caaccatcta aaactccagt tcca                                        24

<210> 76
<211> 28
<212> DNA
<213> Artificial Sequence

<220> 
<223> T6 reverse primer - SNV 11.1 in Fig. 6

<400> 76
tgtgtaacag gacagttgaa tgtagaga                                    28

<210> 77
<211> 19
<212> DNA
<213> Artificial Sequence

<220> 
<223> T7 reverse primer - SNV 13.2 in Fig. 6

<400> 77
cttaaaaccc gccctgcat                                              19

<210> 78
<211> 26
<212> DNA
<213> Artificial Sequence

<220> 
<223> T8 reverse primer - SNV 17.5 in Fig. 6

<400> 78
ctacaggaga tgtggctgtt ctatgt                                      26

<210> 79
<211> 22
<212> DNA
<213> Artificial Sequence

<220> 
<223> T9 reverse primer - SNV 25.8 in Fig. 6

<400> 79
tcagcgtgat tcgcttgtag tc                                          22

<210> 80
<211> 26
<212> DNA
<213> Artificial Sequence

<220> 
<223> T10 reverse primer - SNV 33.0 in Fig. 6

<400> 80
tgcatagctg tttgaataat gacaag                                      26

<210> 81
<211> 21
<212> DNA
<213> Artificial Sequence

<220> 
<223> T11 reverse primer - SNV 38.3 in Fig. 6

<400> 81
tgcagcatct ctgtcaagca a                                           21

<210> 82
<211> 24
<212> DNA
<213> Artificial Sequence

<220> 
<223> T13 reverse primer - SNV 49.6 in Fig. 6

<400> 82
gcaacaacat aacccacagc ataa                                        24

<210> 83
<211> 23
<212> DNA
<213> Artificial Sequence

<220> 
<223> T14 reverse primer - SNV 57.2 in Fig. 6

<400> 83
gctaagcgtt tggaagaaat tcc                                         23

<210> 84
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Forward primer for SV 13.7 in Fig. 6

<400> 84
taggctctaa ggatgctggc                                             20

<210> 85
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Reverse primer for SV 13.7 in Fig. 6

<400> 85
aagcagcttc aaaccctctg                                             20

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

<220> 
<223> Forward primer for SV 20.0 in Fig. 6

<400> 86
ttacttggcc ttggaactgc                                             20

<210> 87
<211> 21
<212> DNA
<213> Artificial Sequence

<220> 
<223> Reverse primer for SV 20.0 in Fig. 6

<400> 87
tgattcgtaa tcgtcactgc c                                           21

<210> 88
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Forward primer for SV 36.9 in Fig. 6

<400> 88
tcctgtcccg agaaactgtc                                             20

<210> 89
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Reverse primer for SV 36.9 in Fig. 6

<400> 89
agctggcttt cagagagctg                                             20

<210> 90
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Forward primer for SV 56.7 in Fig. 6

<400> 90
ttagaaagtg ccaaccaggc                                             20

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

<220> 
<223> Reverse primer for SV 56.7 in Fig. 6

<400> 91
ctctggctag gaacaatggc                                             20

<210> 92
<211> 25
<212> DNA
<213> Artificial Sequence

<220> 
<223> m-lr-f primer for Lrp5 locus

<400> 92
gttaggtgca gggtctactc agctg                                       25

<210> 93
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> m-5'-f primer for Lrp5 locus

<400> 93
ggaggagagg agaagcagcc                                             20

<210> 94
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> m-A primer for Lrp5 locus

<400> 94
ggaggagagg agaagcagcc                                             20

<210> 95
<211> 26
<212> DNA
<213> Artificial Sequence

<220> 
<223> h-lr-r primer for Lrp5 locus

<400> 95
gcaaacagcc ttcttcccac attcgg                                      26

<210> 96
<211> 24
<212> DNA
<213> Artificial Sequence

<220> 
<223> m-5'-r primer for Lrp5 locus

<400> 96
ttgctttcag tagttcaggt gtgc                                        24

<210> 97
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> h-5'-r primer for Lrp5 locus

<400> 97
ggcgttgtca ggaagttgcc                                             20

<210> 98
<211> 22
<212> DNA
<213> Artificial Sequence

<220> 
<223> m-F primer for Lrp5 locus

<400> 98
tgaagttgag aggcacatga gg                                          22

<210> 99
<211> 24
<212> DNA
<213> Artificial Sequence

<220> 
<223> m-E2 primer for Lrp5 locus

<400> 99
tagagtagcc acaggcagca aagc                                        24

<210> 100
<211> 22
<212> DNA
<213> Artificial Sequence

<220> 
<223> 7064retU forward primer

<400> 100
cctcctgagc tttcctttgc ag                                          22

<210> 101
<211> 25
<212> DNA
<213> Artificial Sequence

<220> 
<223> 7064retU reverse primer

<400> 101
cctagacaac acagacactg tatca                                       25

<210> 102
<211> 23
<212> DNA
<213> Artificial Sequence

<220> 
<223> 7064retU TAQMAN probe

<400> 102
ttctgccctt gaaaaggaga ggc                                         23

<210> 103
<211> 18
<212> DNA
<213> Artificial Sequence

<220> 
<223> 7064retD forward primer

<400> 103
cctctgaggc cacctgaa                                               18

<210> 104
<211> 23
<212> DNA
<213> Artificial Sequence

<220> 
<223> 7064retD reverse primer

<400> 104
ccctgacaag ttctgccttc tac                                         23

<210> 105
<211> 21
<212> DNA
<213> Artificial Sequence

<220> 
<223> 7064retD TAQMAN probe

<400> 105
tgcccaagcc tctgcagctt t                                           21

<210> 106
<211> 19
<212> DNA
<213> Artificial Sequence

<220> 
<223> 7140retU forward primer

<400> 106
cccagcatct gacgacacc                                              19

<210> 107
<211> 21
<212> DNA
<213> Artificial Sequence

<220> 
<223> 7140retU reverse primer

<400> 107
gaccactgtg ggcatctgta g                                           21

<210> 108
<211> 27
<212> DNA
<213> Artificial Sequence

<220> 
<223> 7140retU TAQMAN probe

<400> 108
ccgagtctgc tgttactgtt agcatca                                     27

<210> 109
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> 7140retD forward primer

<400> 109
cccgacacct tctgagcatg                                             20

<210> 110
<211> 21
<212> DNA
<213> Artificial Sequence

<220> 
<223> 7140retD reverse primer

<400> 110
tgcaggctga gtcaggattt g                                           21

<210> 111
<211> 25
<212> DNA
<213> Artificial Sequence

<220> 
<223> 7140retD TAQMAN probe

<400> 111
tagtcacgtt ttgtgacacc ccaga                                       25

<210> 112
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Folh1 gRNA A DNA-targeting segment

<400> 112
tgaaccaatt gtgtagcctt                                             20

<210> 113
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Folh1 gRNA A2 DNA-targeting segment

<400> 113
aatagtggta aagcaccatg                                             20

<210> 114
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Folh1 gRNA B DNA-targeting segment

<400> 114
gtgtgctaag gatcgaagtc                                             20

<210> 115
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Folh1 gRNA C DNA-targeting segment

<400> 115
caccgagatg cttgggtatt                                             20

<210> 116
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Folh1 gRNA D DNA-targeting segment

<400> 116
tgtaaccgcc ctgaatgacc                                             20

<210> 117
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Folh1 gRNA E DNA-targeting segment

<400> 117
aaaagggcat cataaatccc                                             20

<210> 118
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Folh1 gRNA E2 DNA-targeting segment

<400> 118
tcaaaaatag tcatacacct                                             20

<210> 119
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Folh1 gRNA F DNA-targeting segment

<400> 119
ggtctctagt acattgtaga                                             20

<210> 120
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Adamts5 gRNA A DNA-targeting segment

<400> 120
ggtggtggtg ctgacggaca                                             20

<210> 121
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Adamts5 gRNA A2 DNA-targeting segment

<400> 121
tatgagatca acactcgcta                                             20

<210> 122
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Adamts5 gRNA B DNA-targeting segment

<400> 122
ccaaggactt ccccacgtta                                             20

<210> 123
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Adamts5 gRNA C DNA-targeting segment

<400> 123
tgcttccctt atgcaagatt                                             20

<210> 124
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Adamts5 gRNA D DNA-targeting segment

<400> 124
ttaggtaccc tatttgaata                                             20

<210> 125
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Adamts5 gRNA E2 DNA-targeting segment

<400> 125
tgcagtgggt gacaggtcca                                             20

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

<220> 
<223> Adamts5 gRNA E DNA-targeting segment

<400> 126
agggttatac tgacgttgtg                                             20

<210> 127
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Adamts5 gRNA F DNA-targeting segment

<400> 127
tgtctttcaa ggagggctac                                             20

<210> 128
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Dpp4 gRNA A DNA-targeting segment

<400> 128
actagtagac ctgaggggtt                                             20

<210> 129
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Dpp4 gRNA B DNA-targeting segment

<400> 129
gctccagtgt ttaggccttg                                             20

<210> 130
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Dpp4 gRNA B2 DNA-targeting segment

<400> 130
ggcaagctga aaacgcatgc                                             20

<210> 131
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Dpp4 gRNA C DNA-targeting segment

<400> 131
gtagatcgct ttccactacc                                             20

<210> 132
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Dpp4 gRNA D DNA-targeting segment

<400> 132
gaactccact gctcgtgagc                                             20

<210> 133
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Dpp4 gRNA E2 DNA-targeting segment

<400> 133
ataggtgggc actattgaag                                             20

<210> 134
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Dpp4 gRNA E DNA-targeting segment

<400> 134
atgggaaggt ttataccagc                                             20

<210> 135
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Dpp4 gRNA F DNA-targeting segment

<400> 135
cggtgtaaaa acaacgggaa                                             20

<210> 136
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Forward primer for SV 6.1 in Fig. 8

<400> 136
ggaatgccaa ggctactgtc                                             20

<210> 137
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Reverse primer for SV 6.1 in Fig. 8

<400> 137
aaaagtctgc tttgggtggt                                             20

<210> 138
<211> 21
<212> DNA
<213> Artificial Sequence

<220> 
<223> Forward primer for SV 6.3 in Fig. 8

<400> 138
cttcatgaac ctcactcagg a                                           21

<210> 139
<211> 21
<212> DNA
<213> Artificial Sequence

<220> 
<223> Reverse primer for SV 6.3 in Fig. 8

<400> 139
tctcggagtc aggatttacc t                                           21

<210> 140
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Forward primer for SV 7.8 in Fig. 8

<400> 140
tgtctctttg cctgttgctg                                             20

<210> 141
<211> 22
<212> DNA
<213> Artificial Sequence

<220> 
<223> Reverse primer for SV 7.8 in Fig. 8

<400> 141
tctgctctac aaggcttacg tg                                          22

<210> 142
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Forward primer for SV 16 in Fig. 8

<400> 142
caaccaggca gacttacagc                                             20

<210> 143
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Reverse primer for SV 16 in Fig. 8

<400> 143
ggcctaggaa ccagtcaaaa                                             20

<210> 144
<211> 23
<212> DNA
<213> Artificial Sequence

<220> 
<223> Forward primer for SV 25.5 in Fig. 8

<400> 144
gcttactgga aagctacata ggg                                         23

<210> 145
<211> 22
<212> DNA
<213> Artificial Sequence

<220> 
<223> Reverse primer for SV 25.5 in Fig. 8

<400> 145
caacaacata gaaacccctg tc                                          22

<210> 146
<211> 6
<212> DNA
<213> Artificial Sequence

<220> 
<223> S. aureus Cas9 PAM sequence

<220> 
<221> misc_feature   
<222> (1)...(2)
<223> n = A, T, C, or G

<220> 
<221> misc_feature   
<222> (4)...(5)
<223> r = A or G

<400> 146
nngrrt                                                            6

<210> 147
<211> 5
<212> DNA
<213> Artificial Sequence

<220> 
<223> S. aureus Cas9 PAM sequence

<220> 
<221> misc_feature   
<222> (1)...(2)
<223> n = A, T, C, or G

<220> 
<221> misc_feature   
<222> (4)...(5)
<223> r = A or G

<400> 147
nngrr                                                             5

<210> 148
<211> 3155
<212> DNA
<213> Artificial Sequence

<220> 
<223> Engineered Human Vk1-39Jk5 Locus

<400> 148
ggcgcgccgt agctttgaat tttaaacatc tatttgacaa gaaatgcata gttccttctc 60
tttaaaataa tgtaatgttt ctttcaagaa taagcttggt ttgatgcctc tctccccaac 120
atgatagaag tgtagcataa atctatgaaa aattccattt ccctgtgcct acaacaacta 180
cctgggattg aaaacttctt cccttgctct agtcctttct tctacaccta cttccacatc 240
atctgtgact caaaacaata cttgtcagga aagatcccgg aaagagcaaa aaagacttcc 300
ttagaggtgt cagagattcc tatgccacta tctgtcatct ctagaagggg ttgtgagtat 360
gaggaagagc agagcttgta aattttctac ttgctttgac ttccactgta tttcctaaca 420
acaacaacca cagcaacacc cataacatca caggacaaac ttctagtact tccaaggctt 480
tagtctcagt aaatcttctc tacctccatc acagcagcta gaaggtttga tactcataca 540
aatagtactg tagctttctg ttcataattg gaaaaataga caagacccaa tgtaatacag 600
gctttccttc agccagttag cgttcagttt ttggatcacc attgcacaca tatacccagc 660
atatgtctaa tatatatgta gaaatccgtg aagcaagagt tataatagct tgtgttttct 720
attgtattgt attttcctct tatatcatct tcttcttcgt tcattaaaaa aaaaccgttc 780
aagtaggtct aaattaatta ttggatcata agtagataaa atattttatt tcataacaca 840
ttgacccgat gaatatgttt ctttgccaga catagtcctc atttccaagg taacaagcct 900
gaaaaaatta tactggagca agtcaacagg taatgatggt agcttttcct tattgtcctg 960
gggcaagaat aagacaaaag ataacagggt agaataaaga ttgtgtaaga aagaaggaca 1020
gcaacaggac atgggaacct tttatagagt aacattttga taatggatga tgagaattaa 1080
tgagttagac agggatgggt gggaatgatt gaaggtgtga gtactttagc acagattaag 1140
accaaatcat taggatttaa agagttgtgt agagttagtg aaggaaaagc cttagaatta 1200
aatttggctg cggataaaac attcttggat tagactgaag actcttttct gtgctaagta 1260
agtatattta tgataatgat gatgactgta gtgctgaata tttaataaat aaaaacaaaa 1320
ttaattgccg catacataat gtcctgaata ctattgtaaa tgttttatct tatttccttt 1380
aaactgtcta cagcactata aggtaggtac cagtattgtc acagttacac agatatggaa 1440
accgagacac agggaagtta agttacttga tcaatttcaa gcaatcggca agccatggag 1500
catctatgtc agggctgcca ggacatgtga ctgtaaacag aagtttttca ctttttaact 1560
caaagagggt atgtggctgg gttaatggaa agcttcagga ccctcagaaa acattactaa 1620
caagcaaatg aaaggtgtat ctggaagatt aagttttaac agactcttca tttccatcga 1680
tccaataatg cacttaggga gatgactggg catattgagg ataggaagag agaagtgaaa 1740
acacagcttt ttatattgtt cttaacaggc ttgtgccaaa catcttctgg gtggatttag 1800
gtgattgagg agaagaaaga cacaggagcg aaattctctg agcacaaggg aggagttcta 1860
cactcagact gagccaacag acttttctgg cctgacaacc agggcggcgc aggatgctca 1920
gtgcagagag gaagaagcag gtggtctttg cagctgaaag ctcagctgat ttgcatatgg 1980
agtcattata caacatccca gaattcttta agggcagctg ccaggaagct aagaagcatc 2040
ctctcttcta gctctcagag atggagacag acacactcct gctatgggtg ctgctgctct 2100
gggttccagg tgagggtaca gataagtgtt atgagcaacc tctgtggcca ttatgatgct 2160
ccatgcctct ctgttcttga tcactataat tagggcattt gtcactggtt ttaagtttcc 2220
ccagtcccct gaattttcca ttttctcaga gtgatgtcca aaattattct taaaaattta 2280
aatgaaaagg tcctctgctg tgaaggcttt taaagatata taaaaataat ctttgtgttt 2340
atcattccag gtgccagatg tgacatccag atgacccagt ctccatcctc cctgtctgca 2400
tctgtaggag acagagtcac catcacttgc cgggcaagtc agagcattag cagctattta 2460
aattggtatc agcagaaacc agggaaagcc cctaagctcc tgatctatgc tgcatccagt 2520
ttgcaaagtg gggtcccatc aaggttcagt ggcagtggat ctgggacaga tttcactctc 2580
accatcagca gtctgcaacc tgaagatttt gcaacttact actgtcaaca gagttacagt 2640
acccctccga tcaccttcgg ccaagggaca cgactggaga ttaaacgtaa gtaatttttc 2700
actattgtct tctgaaattt gggtctgatg gccagtattg acttttagag gcttaaatag 2760
gagtttggta aagattggta aatgagggca tttaagattt gccatgggtt gcaaaagtta 2820
aactcagctt caaaaatgga tttggagaaa aaaagattaa attgctctaa actgaatgac 2880
acaaagtaaa aaaaaaaagt gtaactaaaa aggaaccctt gtatttctaa ggagcaaaag 2940
taaatttatt tttgttcact cttgccaaat attgtattgg ttgttgctga ttatgcatga 3000
tacagaaaag tggaaaaata cattttttag tctttctccc ttttgtttga taaattattt 3060
tgtcagacaa caataaaaat caatagcacg ccctaagatc tagatgcatg ctcgagtgcc 3120
atttcattac ctctttctcc gcacccgaca tagat                            3155

<210> 149
<211> 3166
<212> DNA
<213> Artificial Sequence

<220> 
<223> Engineered Human Vk3-20Jk1 Locus

<400> 149
ggcgcgccgt agctttgaat tttaaacatc tatttgacaa gaaatgcata gttccttctc 60
tttaaaataa tgtaatgttt ctttcaagaa taagcttggt ttgatgcctc tctccccaac 120
atgatagaag tgtagcataa atctatgaaa aattccattt ccctgtgcct acaacaacta 180
cctgggattg aaaacttctt cccttgctct agtcctttct tctacaccta cttccacatc 240
atctgtgact caaaacaata cttgtcagga aagatcccgg aaagagcaaa aaagacttcc 300
ttagaggtgt cagagattcc tatgccacta tctgtcatct ctagaagggg ttgtgagtat 360
gaggaagagc agagcttgta aattttctac ttgctttgac ttccactgta tttcctaaca 420
acaacaacca cagcaacacc cataacatca caggacaaac ttctagtact tccaaggctt 480
tagtctcagt aaatcttctc tacctccatc acagcagcta gaaggtttga tactcataca 540
aatagtactg tagctttctg ttcataattg gaaaaataga caagacccaa tgtaatacag 600
gctttccttc agccagttag cgttcagttt ttggatcacc attgcacaca tatacccagc 660
atatgtctaa tatatatgta gaaatccgtg aagcaagagt tataatagct tgtgttttct 720
attgtattgt attttcctct tatatcatct tcttcttcgt tcattaaaaa aaaaccgttc 780
aagtaggtct aaattaatta ttggatcata agtagataaa atattttatt tcataacaca 840
ttgacccgat gaatatgttt ctttgccaga catagtcctc atttccaagg taacaagcct 900
gaaaaaatta tactggagca agtcaacagg taatgatggt agcttttcct tattgtcctg 960
gggcaagaat aagacaaaag ataacagggt agaataaaga ttgtgtaaga aagaaggaca 1020
gcaacaggac atgggaacct tttatagagt aacattttga taatggatga tgagaattaa 1080
tgagttagac agggatgggt gggaatgatt gaaggtgtga gtactttagc acagattaag 1140
accaaatcat taggatttaa agagttgtgt agagttagtg aaggaaaagc cttagaatta 1200
aatttggctg cggataaaac attcttggat tagactgaag actcttttct gtgctaagta 1260
agtatattta tgataatgat gatgactgta gtgctgaata tttaataaat aaaaacaaaa 1320
ttaattgccg catacataat gtcctgaata ctattgtaaa tgttttatct tatttccttt 1380
aaactgtcta cagcactata aggtaggtac cagtattgtc acagttacac agatatggaa 1440
accgagacac agggaagtta agttacttga tcaatttcaa gcaatcggca agccatggag 1500
catctatgtc agggctgcca ggacatgtga ctgtaaacag aagtttttca ctttttaact 1560
caaagagggt atgtggctgg gttaatggaa agcttcagga ccctcagaaa acattactaa 1620
caagcaaatg aaaggtgtat ctggaagatt aagttttaac agactcttca tttccatcga 1680
tccaataatg cacttaggga gatgactggg catattgagg ataggaagag agaagtgaaa 1740
acacagcttt ttatattgtt cttaacaggc ttgtgccaaa catcttctgg gtggatttag 1800
gtgattgagg agaagaaaga cacaggagcg aaattctctg agcacaaggg aggagttcta 1860
cactcagact gagccaacag acttttctgg cctgacaacc agggcggcgc aggatgctca 1920
gtgcagagag gaagaagcag gtggtctttg cagctgaaag ctcagctgat ttgcatatgg 1980
agtcattata caacatccca gaattcttta agggcagctg ccaggaagct aagaagcatc 2040
ctctcttcta gctctcagag atggagacag acacactcct gctatgggtg ctgctgctct 2100
gggttccagg tgagggtaca gataagtgtt atgagcaacc tctgtggcca ttatgatgct 2160
ccatgcctct ctgttcttga tcactataat tagggcattt gtcactggtt ttaagtttcc 2220
ccagtcccct gaattttcca ttttctcaga gtgatgtcca aaattattct taaaaattta 2280
aatgaaaagg tcctctgctg tgaaggcttt taaagatata taaaaataat ctttgtgttt 2340
atcattccag gtgccagatg tataccaccg gagaaattgt gttgacgcag tctccaggca 2400
ccctgtcttt gtctccaggg gaaagagcca ccctctcctg cagggccagt cagagtgtta 2460
gcagcagcta cttagcctgg taccagcaga aacctggcca ggctcccagg ctcctcatct 2520
atggtgcatc cagcagggcc actggcatcc cagacaggtt cagtggcagt gggtctggga 2580
cagacttcac tctcaccatc agcagactgg agcctgaaga ttttgcagtg tattactgtc 2640
agcagtatgg tagctcacct tggacgttcg gccaagggac caaggtggaa atcaaacgta 2700
agtaattttt cactattgtc ttctgaaatt tgggtctgat ggccagtatt gacttttaga 2760
ggcttaaata ggagtttggt aaagattggt aaatgagggc atttaagatt tgccatgggt 2820
tgcaaaagtt aaactcagct tcaaaaatgg atttggagaa aaaaagatta aattgctcta 2880
aactgaatga cacaaagtaa aaaaaaaaag tgtaactaaa aaggaaccct tgtatttcta 2940
aggagcaaaa gtaaatttat ttttgttcac tcttgccaaa tattgtattg gttgttgctg 3000
attatgcatg atacagaaaa gtggaaaaat acatttttta gtctttctcc cttttgtttg 3060
ataaattatt ttgtcagaca acaataaaaa tcaatagcac gccctaagat ctagatgcat 3120
gctcgagtgc catttcatta cctctttctc cgcacccgac atagat                3166

<210> 150
<211> 82
<212> DNA
<213> Artificial Sequence

<220> 
<223> Guide RNA Scaffold v1

<400> 150
gttggaacca ttcaaaacag catagcaagt taaaataagg ctagtccgtt atcaacttga 60
aaaagtggca ccgagtcggt gc                                          82

<210> 151
<211> 76
<212> DNA
<213> Artificial Sequence

<220> 
<223> Guide RNA Scaffold v2

<400> 151
gttttagagc tagaaatagc aagttaaaat aaggctagtc cgttatcaac ttgaaaaagt 60
ggcaccgagt cggtgc                                                 76

<210> 152
<211> 86
<212> DNA
<213> Artificial Sequence

<220> 
<223> Guide RNA Scaffold v3

<400> 152
gtttaagagc tatgctggaa acagcatagc aagtttaaat aaggctagtc cgttatcaac 60
ttgaaaaagt ggcaccgagt cggtgc                                      86
