                         SEQUENCE LISTING

<110>  bluebird bio, Inc.
       Jarjour, Jordan
       Havens, Kyle
       Chrysostomou, Constantine
 
<120>  HOMING ENDONUCLEASE VARIANTS

<130>  BLUE-110.PC

<150>  US 62/777,476
<151>  2018-12-10

<160>  59    

<170>  PatentIn version 3.5

<210>  1
<211>  303
<212>  PRT
<213>  Ophiostoma novo-ulmi

<400>  1

Met Ala Tyr Met Ser Arg Arg Glu Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Leu Leu Arg Ile Arg Asn Asn 
            20                  25                  30          


Asn Lys Ser Ser Val Gly Tyr Ser Thr Glu Leu Gly Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Val Ile Ala Asn Ser Gly Asp Asn Ala Val Ser Leu Lys 
65                  70                  75                  80  


Val Thr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Met Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Cys Val Met Glu Asn Lys Glu His Leu Lys Ile Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Leu Asn Trp Gly Leu Thr Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Ile Ile Ser Lys Glu Arg Ser Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Phe Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Glu Gly Cys Phe Phe Val Asn Leu Ile Lys Ser Lys Ser Lys Leu 
            180                 185                 190         


Gly Val Gln Val Gln Leu Val Phe Ser Ile Thr Gln His Ile Lys Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly Tyr Ile 
    210                 215                 220                 


Lys Glu Lys Asn Lys Ser Glu Phe Ser Trp Leu Asp Phe Val Val Thr 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg Val Phe 
    290                 295                 300             


<210>  2
<211>  303
<212>  PRT
<213>  Ophiostoma novo-ulmi

<400>  2

Met Ala Tyr Met Ser Arg Arg Glu Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Leu Leu Arg Ile Arg Asn Asn 
            20                  25                  30          


Asn Lys Ser Ser Val Gly Tyr Ser Thr Glu Leu Gly Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Val Ile Ala Asn Ser Gly Asp Asn Ala Val Ser Leu Lys 
65                  70                  75                  80  


Val Thr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Leu Asn Trp Gly Leu Thr Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Ser Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Phe Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Glu Gly Cys Phe Phe Val Asn Leu Ile Lys Ser Lys Ser Lys Leu 
            180                 185                 190         


Gly Val Gln Val Gln Leu Val Phe Ser Ile Thr Gln His Ile Lys Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly Tyr Ile 
    210                 215                 220                 


Lys Glu Lys Asn Lys Ser Glu Phe Ser Trp Leu Asp Phe Val Val Thr 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg Val Phe 
    290                 295                 300             


<210>  3
<211>  303
<212>  PRT
<213>  Ophiostoma novo-ulmi


<220>
<221>  MOD_RES
<222>  (1)..(3)
<223>  Any amino acid or absent

<400>  3

Xaa Xaa Xaa Met Ser Arg Arg Glu Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Leu Leu Arg Ile Arg Asn Asn 
            20                  25                  30          


Asn Lys Ser Ser Val Gly Tyr Ser Thr Glu Leu Gly Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Val Ile Ala Asn Ser Gly Asp Asn Ala Val Ser Leu Lys 
65                  70                  75                  80  


Val Thr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Leu Asn Trp Gly Leu Thr Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Ser Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Phe Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Glu Gly Cys Phe Phe Val Asn Leu Ile Lys Ser Lys Ser Lys Leu 
            180                 185                 190         


Gly Val Gln Val Gln Leu Val Phe Ser Ile Thr Gln His Ile Lys Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly Tyr Ile 
    210                 215                 220                 


Lys Glu Lys Asn Lys Ser Glu Phe Ser Trp Leu Asp Phe Val Val Thr 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg Val Phe 
    290                 295                 300             


<210>  4
<211>  303
<212>  PRT
<213>  Ophiostoma novo-ulmi


<220>
<221>  MOD_RES
<222>  (1)..(4)
<223>  Any amino acid or absent

<220>
<221>  MOD_RES
<222>  (302)..(303)
<223>  Any amino acid or absent

<400>  4

Xaa Xaa Xaa Xaa Ser Arg Arg Glu Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Leu Leu Arg Ile Arg Asn Asn 
            20                  25                  30          


Asn Lys Ser Ser Val Gly Tyr Ser Thr Glu Leu Gly Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Val Ile Ala Asn Ser Gly Asp Asn Ala Val Ser Leu Lys 
65                  70                  75                  80  


Val Thr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Leu Asn Trp Gly Leu Thr Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Ser Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Phe Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Glu Gly Cys Phe Phe Val Asn Leu Ile Lys Ser Lys Ser Lys Leu 
            180                 185                 190         


Gly Val Gln Val Gln Leu Val Phe Ser Ile Thr Gln His Ile Lys Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly Tyr Ile 
    210                 215                 220                 


Lys Glu Lys Asn Lys Ser Glu Phe Ser Trp Leu Asp Phe Val Val Thr 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg Xaa Xaa 
    290                 295                 300             


<210>  5
<211>  303
<212>  PRT
<213>  Ophiostoma novo-ulmi


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<220>
<221>  MOD_RES
<222>  (302)..(303)
<223>  Any amino acid or absent

<400>  5

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Leu Leu Arg Ile Arg Asn Asn 
            20                  25                  30          


Asn Lys Ser Ser Val Gly Tyr Ser Thr Glu Leu Gly Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Val Ile Ala Asn Ser Gly Asp Asn Ala Val Ser Leu Lys 
65                  70                  75                  80  


Val Thr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Leu Asn Trp Gly Leu Thr Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Ser Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Phe Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Glu Gly Cys Phe Phe Val Asn Leu Ile Lys Ser Lys Ser Lys Leu 
            180                 185                 190         


Gly Val Gln Val Gln Leu Val Phe Ser Ile Thr Gln His Ile Lys Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly Tyr Ile 
    210                 215                 220                 


Lys Glu Lys Asn Lys Ser Glu Phe Ser Trp Leu Asp Phe Val Val Thr 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg Xaa Xaa 
    290                 295                 300             


<210>  6
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  6

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Ile Leu Asp Ile Arg Asn Arg 
            20                  25                  30          


Asn Asn Glu Ser Asn Arg Tyr Arg Thr Ser Leu Arg Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Lys Ile Thr Asn Ser Ser Asp Arg Ala Val Met Leu Arg 
65                  70                  75                  80  


Val Thr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Pro Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Phe Lys Trp Leu Ala Gly Phe Thr Ala 
                165                 170                 175     


Gly Asp Gly His Phe Gly Val Asn Leu Lys Lys Val Lys Gly Thr Ala 
            180                 185                 190         


Lys Val Tyr Val Gly Leu Arg Phe Ala Ile Ser Gln His Ile Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly Ser Ile 
    210                 215                 220                 


Arg Glu Lys Asn Lys Ser Glu Phe Arg Trp Leu Glu Phe Glu Val Thr 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg 
    290                 295                 300     


<210>  7
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  7

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Cys Phe Arg Leu Asp Ile Arg Asn Ala 
            20                  25                  30          


Asn Asp Leu Arg Ala Gly Tyr Arg Thr Arg Leu Ala Phe Glu Ile Val 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Thr Ile Tyr Asn Ala Gly Asp Asn Ala Val Arg Leu Gln 
65                  70                  75                  80  


Val Thr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Ser Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Leu Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Val Val Glu Leu Lys Lys Arg Arg Ser Pro Val 
            180                 185                 190         


Lys Val Gly Val Arg Leu Arg Phe Ser Ile Thr Gln His Ile Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly Arg Ile 
    210                 215                 220                 


Val Glu Asn Asn Lys Ser Glu His Ser Trp Leu Glu Phe Ile Val Thr 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg 
    290                 295                 300     


<210>  8
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  8

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Cys Phe Arg Leu Asp Ile Arg Asn Ala 
            20                  25                  30          


Asn Asp Leu Arg Ala Gly Tyr Arg Thr Arg Leu Ala Phe Glu Ile Val 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Thr Ile Tyr Asn Ala Gly Asp Asn Ala Val Arg Leu Gln 
65                  70                  75                  80  


Val Thr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Ser Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Leu Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Val Val Glu Leu Lys Lys Arg Arg Ser Pro Val 
            180                 185                 190         


Lys Val Gly Val Arg Leu Arg Phe Ser Ile Thr Gln His Ile Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly Arg Ile 
    210                 215                 220                 


Val Glu Asn Asn Lys Ser Glu His Ser Trp Leu Glu Phe Ile Val Thr 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg 
    290                 295                 300     


<210>  9
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE thermostable variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  9

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Val Leu Ser Ile Gln Asn Arg 
            20                  25                  30          


Asn Asp Tyr Ala Thr Gly Tyr Arg Ile His Leu Thr Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Lys Ile Asn Asn Thr Gly Asp Asn Leu Val Gln Leu Arg 
65                  70                  75                  80  


Val Tyr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Pro Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Ser Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Phe Val Arg Leu Arg Lys Ser Asn Val Asn Ala 
            180                 185                 190         


Arg Val Arg Val Gln Leu Val Phe Glu Ile Ser Gln His Ile Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly His Ile 
    210                 215                 220                 


Tyr Glu Gly Asn Lys Ser Glu Arg Ser Trp Leu Gln Phe Arg Val Glu 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg 
    290                 295                 300     


<210>  10
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE thermostable variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  10

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Thr Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Val Leu Ser Ile Gln Asn Arg 
            20                  25                  30          


Asn Asp Tyr Ala Thr Gly Tyr Arg Ile His Leu Thr Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Lys Ile Asn Asn Thr Gly Asp Asn Leu Val Gln Leu Arg 
65                  70                  75                  80  


Val Tyr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Pro Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Phe Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Phe Val Arg Leu Arg Lys Ser Asn Val Asn Ala 
            180                 185                 190         


Arg Val Arg Val Gln Leu Val Phe Glu Ile Ser Gln His Ile Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly His Ile 
    210                 215                 220                 


Tyr Glu Gly Asn Lys Ser Glu Arg Ser Trp Leu Gln Phe Arg Val Glu 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg 
    290                 295                 300     


<210>  11
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE thermostable variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  11

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Val Leu Ser Ile Gln Asn Arg 
            20                  25                  30          


Asn Asp Tyr Ala Thr Gly Tyr Arg Ile His Leu Thr Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Lys Ile Asn Asn Thr Gly Asp Asn Leu Val Gln Leu Arg 
65                  70                  75                  80  


Val Tyr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Pro Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Phe Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Phe Val Arg Leu Arg Lys Ser Asn Val Asn Ala 
            180                 185                 190         


Arg Val Arg Val Gln Leu Val Phe Glu Ile Ser Gln His Ile Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly His Ile 
    210                 215                 220                 


Tyr Glu Gly Asn Lys Ser Glu Arg Ser Trp Leu Gln Phe Arg Val Glu 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Ile Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg 
    290                 295                 300     


<210>  12
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE thermostable variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  12

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Val Leu Ser Ile Gln Asn Arg 
            20                  25                  30          


Asn Asp Tyr Ala Thr Gly Tyr Arg Ile His Leu Thr Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Lys Ile Asn Asn Thr Gly Asp Asn Leu Val Gln Leu Arg 
65                  70                  75                  80  


Val Tyr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Pro Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Phe Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Phe Val Arg Leu Arg Lys Ser Asn Val Asn Ala 
            180                 185                 190         


Arg Val Arg Val Gln Leu Val Phe Glu Ile Ser Gln His Ile Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly His Ile 
    210                 215                 220                 


Tyr Glu Gly Asn Lys Ser Glu Arg Ser Trp Leu Gln Phe Arg Val Glu 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Ala Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg 
    290                 295                 300     


<210>  13
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE thermostable variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  13

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Val Leu Ser Ile Gln Asn Arg 
            20                  25                  30          


Asn Asp Tyr Ala Thr Gly Tyr Arg Ile His Leu Thr Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Lys Ile Asn Asn Thr Gly Asp Asn Leu Val Gln Leu Arg 
65                  70                  75                  80  


Val Tyr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Pro Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Phe Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Phe Val Arg Leu Arg Lys Ser Asn Val Asn Ala 
            180                 185                 190         


Arg Val Arg Val Arg Leu Val Phe Glu Ile Ser Gln His Val Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly His Ile 
    210                 215                 220                 


Tyr Glu Gly Asn Lys Ser Glu Arg Ser Trp Leu Gln Phe Arg Val Glu 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Ile Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Ala Lys His Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg 
    290                 295                 300     


<210>  14
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE thermostable variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  14

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Thr Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Val Leu Ser Ile Gln Asn Arg 
            20                  25                  30          


Asn Asp Tyr Ala Thr Gly Tyr Arg Ile His Leu Thr Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Lys Ile Asn Asn Thr Gly Asp Asn Leu Val Gln Leu Arg 
65                  70                  75                  80  


Val Tyr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Val Ile Ser Arg Glu Arg Pro Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Gly Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Phe Val Arg Leu Arg Lys Ser Asn Val Asn Ala 
            180                 185                 190         


Arg Val Arg Val Gln Leu Val Phe Glu Ile Ser Gln His Ile Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly His Ile 
    210                 215                 220                 


Tyr Glu Gly Asn Lys Ser Glu Arg Ser Trp Leu Gln Phe Arg Val Glu 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Met Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Arg Arg 
    290                 295                 300     


<210>  15
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  15

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Ile Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Gly Leu Ser Ile Leu Asn Arg 
            20                  25                  30          


Asn Arg Gly Thr Ala Arg Tyr His Thr Arg Leu Ser Phe Thr Ile Met 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Ser Ile Leu Asn Asn Gly Asp His Tyr Val Ser Leu Val 
65                  70                  75                  80  


Val Tyr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Pro Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Phe Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Phe Val Arg Leu Arg Lys Ser Asn Val Asn Ala 
            180                 185                 190         


Arg Val Arg Val Gln Leu Val Phe Glu Ile Ser Gln His Ile Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly His Ile 
    210                 215                 220                 


Tyr Glu Gly Asn Lys Ser Glu Arg Ser Trp Leu Gln Phe Arg Val Glu 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg 
    290                 295                 300     


<210>  16
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE thermostable variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  16

Xaa Xaa Xaa Xaa Ser Arg Arg Glu Ser Ile Asn Pro Trp Thr Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Gly Leu Ser Ile Leu Asn Arg 
            20                  25                  30          


Asn Arg Gly Thr Ala Arg Tyr His Thr Arg Leu Ser Phe Thr Ile Met 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Ser Ile Leu Asn Asn Gly Asp His Tyr Val Ser Leu Val 
65                  70                  75                  80  


Val Tyr Ala Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Val Ile Ser Arg Glu Arg Pro Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Gly Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Phe Val Arg Leu Arg Lys Ser Asn Val Asn Ala 
            180                 185                 190         


Arg Val Arg Val Gln Leu Val Phe Glu Ile Ser Gln His Ile Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly His Ile 
    210                 215                 220                 


Tyr Glu Gly Asn Lys Ser Glu Arg Ser Trp Leu Gln Phe Arg Val Glu 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Met Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Arg Arg 
    290                 295                 300     


<210>  17
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE thermostable variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  17

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Thr Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Ser Phe Ile Leu Asp Ile Arg Asn Arg 
            20                  25                  30          


Asn Asn Glu Ser Asn Arg Tyr Arg Thr Ser Leu Arg Phe Gln Ile Thr 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Lys Ile Thr Asn Ser Ser Asp Arg Ala Val Met Leu Arg 
65                  70                  75                  80  


Val Thr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Val Ile Ser Arg Glu Arg Pro Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Gly Lys Trp Leu Ala Gly Phe Thr Ala 
                165                 170                 175     


Gly Asp Gly His Phe Gly Val Asn Leu Lys Lys Val Lys Gly Thr Ala 
            180                 185                 190         


Lys Val Tyr Val Gly Leu Arg Phe Ala Ile Ser Gln His Ile Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly Ser Ile 
    210                 215                 220                 


Arg Glu Lys Asn Lys Ser Glu Phe Arg Trp Leu Glu Phe Glu Val Thr 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Met Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Arg Arg 
    290                 295                 300     


<210>  18
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - reprogrammed I-OnuI LHE thermostable variant


<220>
<221>  MOD_RES
<222>  (1)..(8)
<223>  Any amino acid or absent

<400>  18

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ser Ile Asn Pro Trp Thr Leu Thr 
1               5                   10                  15      


Gly Phe Ala Asp Ala Glu Gly Cys Phe Arg Leu Asp Ile Arg Asn Ala 
            20                  25                  30          


Asn Asp Leu Arg Ala Gly Tyr Arg Thr Arg Leu Ala Phe Glu Ile Val 
        35                  40                  45              


Leu His Asn Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp 
    50                  55                  60                  


Lys Val Gly Thr Ile Tyr Asn Ala Gly Asp Asn Ala Val Arg Leu Gln 
65                  70                  75                  80  


Val Thr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys 
                85                  90                  95      


Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln 
            100                 105                 110         


Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile 
        115                 120                 125             


Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp 
    130                 135                 140                 


Glu Leu Lys Lys Ala Phe Pro Glu Val Ile Ser Arg Glu Arg Ser Leu 
145                 150                 155                 160 


Ile Asn Lys Asn Ile Pro Asn Gly Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Val Val Glu Leu Lys Lys Arg Arg Ser Pro Val 
            180                 185                 190         


Lys Val Gly Val Arg Leu Arg Phe Ser Ile Thr Gln His Ile Arg Asp 
        195                 200                 205             


Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly Arg Ile 
    210                 215                 220                 


Val Glu Asn Asn Lys Ser Glu His Ser Trp Leu Glu Phe Ile Val Thr 
225                 230                 235                 240 


Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn 
                245                 250                 255     


Thr Leu Ile Gly Met Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val 
            260                 265                 270         


Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp 
        275                 280                 285             


Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Arg Arg 
    290                 295                 300     


<210>  19
<211>  1743
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Made in Lab - BCL11A I-OnuI HE variant codon optimized mRNA

<400>  19
augggaucac cgccuaagaa gaagagaaaa gugucgagaa gggaaucaau uaacccuugg       60

auccugaccg gcuucgccga cgccgagggg ucauuccucc uccgcauucg caauaauaac      120

aagaguagcg uaggcuacuc uacugagcug ggcuuccaga uuacccucca caacaaggac      180

aagaguaucc uggaaaacau ccagucgacu uggaaggugg gcguaauagc uaacagugga      240

gacaacgcug ugucacucaa agucaccagg uucgaggacc ugaaggugau cauugaccac      300

uucgagaagu acccacugau cacucagaag cugggugacu acaagcuguu caagcaagca      360

uuuucgguga uggagaacaa agagcaccug aaggaaaaug gaauuaagga acuugugcgc      420

aucaaggcca aguugaacug gggacuuacg gaugagcuca agaaagcguu uccugaaaac      480

aucucgaaag agaggagucu gauuaacaag aauaucccua acuucaagug gcuggccggg      540

uucacguccg gggaaggaug cuuuuucguc aaccucauaa aaagcaaguc uaaacuugga      600

gugcaagugc agcugguguu uucaaucacu caacacauca aagacaagaa ccucaugaac      660

ucgcucauca ccuaccuggg uugcggauau aucaaagaga aaaacaaguc agaauuuucc      720

uggcuggauu ucguggugac aaaguucagc gacaucaacg acaagaucau cccgguguuc      780

caggagaaca cccucaucgg cgugaagcug gaggacuucg aagauuggug caagguggcg      840

aagcuuaucg aagaaaagaa gcaccugacc gaguccggac uggacgagau caagaagauc      900

aaacugaaca ugaacaaggg ccggagauau ccauacgaug ucccagauua ugcgcucgag      960

aguggggaag gucgcggcuc cuugcucacc uguggggaug ucgaagaaaa cccagguccc     1020

gcuagcguga gcaagggcga ggagcuguuc accggggugg ugcccauccu ggucgagcug     1080

gacggcgacg uaaacggcca caaguucagc guguccggcg agggcgaggg cgaugccacc     1140

uacggcaagc ugacccugaa guucaucugc accaccggca agcugcccgu gcccuggccc     1200

acccucguga ccacccugac cuacggcgug cagugcuuca gccgcuaccc cgaccacaug     1260

aagcagcacg acuucuucaa guccgccaug cccgaaggcu acguccagga gcgcaccauc     1320

uucuucaagg acgacggcaa cuacaagacc cgcgccgagg ugaaguucga gggcgacacc     1380

cuggugaacc gcaucgagcu gaagggcauc gacuucaagg aggacggcaa cauccugggg     1440

cacaagcugg aguacaacua caacagccac aacgucuaua ucauggccga caagcagaag     1500

aacggcauca aggugaacuu caagauccgc cacaacaucg aggacggcag cgugcagcuc     1560

gccgaccacu accagcagaa cacccccauc ggcgacggcc ccgugcugcu gcccgacaac     1620

cacuaccuga gcacccaguc cgcccugagc aaagacccca acgagaagcg cgaucacaug     1680

guccugcugg aguucgugac cgccgccggg aucacucucg gcauggacga gcuguacaag     1740

uga                                                                   1743


<210>  20
<211>  1743
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Made in Lab - BCL11A I-OnuI HE variant mRNA

<400>  20
augggaucac cgccuaagaa gaagagaaaa gugucgagaa gggaauccau caacccaugg       60

auucugacug guuucgcuga ugccgaagga agcuucgugc uaaguaucca aaacagaaac      120

gauuaugcua cugguuacag aauucaccug acauuccaaa ucacccugca caacaaggac      180

aaaucgauuc uggagaauau ccagucgacu uggaaggucg gcaaaaucaa uaacacgggc      240

gacaaccucg uccaacugag agucuaccgu uucgaagauu ugaaagugau uaucgaccac      300

uucgagaaau auccgcugau aacacagaaa uugggcgauu acaaguuguu uaaacaggca      360

uucagcguca uggagaacaa agaacaucuu aaggagaaug ggauuaagga gcucguacga      420

aucaaagcua agaugaauug gggucucaau gacgaauuga aaaaagcauu uccagagaac      480

auuagcaaag agcgcccccu uaucaauaag aacauuccga auuucaaaug gcuggcugga      540

uucacaucug gugauggcuc cuucuucgug cgccuaagaa agucuaaugu uaaugcuaga      600

guacgugugc aacugguauu cgagaucuca cagcacauca gagacaagaa ccugaugaau      660

ucauugauaa cauaccuagg cuguggucac aucuacgagg gaaacaaauc ugagcgcagu      720

uggcuccaau ucagaguaga aaaauucagc gauaucaacg acaagaucau uccgguauuc      780

caggaaaaua cucugauugg cgucaaacuc gaggacuuug aagauuggug caagguugcc      840

aaauugaucg aagagaagaa acaccugacc gaauccgguu uggaugagau uaagaaaauc      900

aagcugaaca ugaacaaagg ucguagauau ccauacgaug ucccagauua ugcgcucgag      960

aguggggaag gucgcggcuc cuugcucacc uguggggaug ucgaagaaaa cccagguccc     1020

gcuagcguga gcaagggcga ggagcuguuc accggggugg ugcccauccu ggucgagcug     1080

gacggcgacg uaaacggcca caaguucagc guguccggcg agggcgaggg cgaugccacc     1140

uacggcaagc ugacccugaa guucaucugc accaccggca agcugcccgu gcccuggccc     1200

acccucguga ccacccugac cuacggcgug cagugcuuca gccgcuaccc cgaccacaug     1260

aagcagcacg acuucuucaa guccgccaug cccgaaggcu acguccagga gcgcaccauc     1320

uucuucaagg acgacggcaa cuacaagacc cgcgccgagg ugaaguucga gggcgacacc     1380

cuggugaacc gcaucgagcu gaagggcauc gacuucaagg aggacggcaa cauccugggg     1440

cacaagcugg aguacaacua caacagccac aacgucuaua ucauggccga caagcagaag     1500

aacggcauca aggugaacuu caagauccgc cacaacaucg aggacggcag cgugcagcuc     1560

gccgaccacu accagcagaa cacccccauc ggcgacggcc ccgugcugcu gcccgacaac     1620

cacuaccuga gcacccaguc cgcccugagc aaagacccca acgagaagcg cgaucacaug     1680

guccugcugg aguucgugac cgccgccggg aucacucucg gcauggacga gcuguacaag     1740

uga                                                                   1743


<210>  21
<211>  1743
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Made in Lab - BCL11A I-OnuI HE A5 variant mRNA

<400>  21
augggaucac cgccuaagaa gaagagaaaa gugucgagaa gggaauccau caacccaugg       60

acucugacug guuucgcuga ugccgaagga agcuucgugc uaaguaucca aaacagaaac      120

gauuaugcua cugguuacag aauucaccug acauuccaaa ucacccugca caacaaggac      180

aaaucgauuc uggagaauau ccagucgacu uggaaggucg gcaaaaucaa uaacacgggc      240

gacaaccucg uccaacugag agucuaccgu uucgaagauu ugaaagugau uaucgaccac      300

uucgagaaau auccgcugau aacacagaaa uugggcgauu acaaauuguu uaaacaggca      360

uucagcguca uggagaacaa agaacaucuu aaggagaaug ggauuaagga gcucguacga      420

aucaaagcua agaugaauug gggucucaau gacgaauuga aaaaagcauu uccagaggug      480

auuagcaggg agcgcccccu uaucaauaag aacauuccga augggaaaug gcuggcugga      540

uucacaucug gugauggcuc cuucuucgug cgccuaagaa agucuaaugu uaaugcuaga      600

guacgugugc aacugguauu cgagaucuca cagcacauca gagauaagaa ccugaugaau      660

ucauugauaa cauaccuagg cuguggucac aucuacgagg gaaacaaauc ugagcgcucu      720

uggcuccaau ucagaguaga aaaauucagc gauaucaaug acaagaucau uccgguauuc      780

caggaaaaua cucugauugg caugaaacuc gaggacuuug aagauuggug caagguugcc      840

aaauugaucg aagagaagaa acaccugacc gaauccgguu uggaugagau uaagaaaauc      900

aagcugaaca ugaacaaaag acguagauau ccauacgaug ucccagauua ugcgcucgag      960

aguggggaag gucgcggcuc cuugcucacc uguggggaug ucgaagaaaa cccagguccc     1020

gcuagcguga gcaagggcga ggagcuguuc accggggugg ugcccauccu ggucgagcug     1080

gacggcgacg uaaacggcca caaguucagc guguccggcg agggcgaggg cgaugccacc     1140

uacggcaagc ugacccugaa guucaucugc accaccggca agcugcccgu gcccuggccc     1200

acccucguga ccacccugac cuacggcgug cagugcuuca gccgcuaccc cgaccacaug     1260

aagcagcacg acuucuucaa guccgccaug cccgaaggcu acguccagga gcgcaccauc     1320

uucuucaagg acgacggcaa cuacaagacc cgcgccgagg ugaaguucga gggcgacacc     1380

cuggugaacc gcaucgagcu gaagggcauc gacuucaagg aggacggcaa cauccugggg     1440

cacaagcugg aguacaacua caacagccac aacgucuaua ucauggccga caagcagaag     1500

aacggcauca aggugaacuu caagauccgc cacaacaucg aggacggcag cgugcagcuc     1560

gccgaccacu accagcagaa cacccccauc ggcgacggcc ccgugcugcu gcccgacaac     1620

cacuaccuga gcacccaguc cgcccugagc aaagacccca acgagaagcg cgaucacaug     1680

guccugcugg aguucgugac cgccgccggg aucacucucg gcauggacga gcuguacaag     1740

uga                                                                   1743


<210>  22
<211>  944
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - engineered PDCD-1 megaTAL

<400>  22

Met Gly Ser Cys Arg Pro Pro Lys Lys Lys Arg Lys Val Val Asp Leu 
1               5                   10                  15      


Arg Thr Leu Gly Tyr Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro Lys 
            20                  25                  30          


Val Arg Ser Thr Val Ala Gln His His Glu Ala Leu Val Gly His Gly 
        35                  40                  45              


Phe Thr His Ala His Ile Val Ala Leu Ser Gln His Pro Ala Ala Leu 
    50                  55                  60                  


Gly Thr Val Ala Val Thr Tyr Gln His Ile Ile Thr Ala Leu Pro Glu 
65                  70                  75                  80  


Ala Thr His Glu Asp Ile Val Gly Val Gly Lys Gln Trp Ser Gly Ala 
                85                  90                  95      


Arg Ala Leu Glu Ala Leu Leu Thr Asp Ala Gly Glu Leu Arg Gly Pro 
            100                 105                 110         


Pro Leu Gln Leu Asp Thr Gly Gln Leu Val Lys Ile Ala Lys Arg Gly 
        115                 120                 125             


Gly Val Thr Ala Met Glu Ala Val His Ala Ser Arg Asn Ala Leu Thr 
    130                 135                 140                 


Gly Ala Pro Leu Asn Leu Thr Pro Asp Gln Val Val Ala Ile Ala Ser 
145                 150                 155                 160 


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


Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln Val Val Ala Ile 
            180                 185                 190         


Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu 
        195                 200                 205             


Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln Val Val 
    210                 215                 220                 


Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln 
225                 230                 235                 240 


Arg Leu Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln 
                245                 250                 255     


Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr 
            260                 265                 270         


Val Gln Arg Leu Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro 
        275                 280                 285             


Asp Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu 
    290                 295                 300                 


Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Asp His Gly Leu 
305                 310                 315                 320 


Thr Pro Asp Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln 
                325                 330                 335     


Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Asp His 
            340                 345                 350         


Gly Leu Thr Pro Asp Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly 
        355                 360                 365             


Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln 
    370                 375                 380                 


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


Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu 
                405                 410                 415     


Cys Gln Asp His Gly Leu Thr Pro Asp Gln Val Val Ala Ile Ala Ser 
            420                 425                 430         


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


Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln Val Val Ala Ile 
    450                 455                 460                 


Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu 
465                 470                 475                 480 


Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln Val Val 
                485                 490                 495     


Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln 
            500                 505                 510         


Arg Leu Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln 
        515                 520                 525             


Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr 
    530                 535                 540                 


Val Gln Arg Leu Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro 
545                 550                 555                 560 


Asp Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu 
                565                 570                 575     


Glu Ser Ile Val Ala Gln Leu Ser Arg Pro Asp Pro Ala Leu Ala Ala 
            580                 585                 590         


Leu Thr Asn Asp His Leu Val Ala Leu Ala Cys Leu Gly Gly Arg Pro 
        595                 600                 605             


Ala Met Asp Ala Val Lys Lys Gly Leu Pro His Ala Pro Glu Leu Ile 
    610                 615                 620                 


Arg Arg Val Asn Arg Arg Ile Gly Glu Arg Thr Ser His Arg Val Ala 
625                 630                 635                 640 


Ile Ser Arg Val Gly Gly Ser Ser Arg Arg Glu Ser Ile Asn Pro Trp 
                645                 650                 655     


Ile Leu Thr Gly Phe Ala Asp Ala Glu Gly Ser Phe Gly Leu Ser Ile 
            660                 665                 670         


Leu Asn Arg Asn Arg Gly Thr Ala Arg Tyr His Thr Arg Leu Ser Phe 
        675                 680                 685             


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


Ser Thr Trp Lys Val Gly Ser Ile Leu Asn Asn Gly Asp His Tyr Val 
705                 710                 715                 720 


Ser Leu Val Val Tyr Arg Phe Glu Asp Leu Lys Val Ile Ile Asp His 
                725                 730                 735     


Phe Glu Lys Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu 
            740                 745                 750         


Phe Lys Gln Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu 
        755                 760                 765             


Asn Gly Ile Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly 
    770                 775                 780                 


Leu Asn Asp Glu Leu Lys Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu 
785                 790                 795                 800 


Arg Pro Leu Ile Asn Lys Asn Ile Pro Asn Phe Lys Trp Leu Ala Gly 
                805                 810                 815     


Phe Thr Ser Gly Asp Gly Ser Phe Phe Val Arg Leu Arg Lys Ser Asn 
            820                 825                 830         


Val Asn Ala Arg Val Arg Val Gln Leu Val Phe Glu Ile Ser Gln His 
        835                 840                 845             


Ile Arg Asp Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys 
    850                 855                 860                 


Gly His Ile Tyr Glu Gly Asn Lys Ser Glu Arg Ser Trp Leu Gln Phe 
865                 870                 875                 880 


Arg Val Glu Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe 
                885                 890                 895     


Gln Glu Asn Thr Leu Ile Gly Val Lys Leu Glu Asp Phe Glu Asp Trp 
            900                 905                 910         


Cys Lys Val Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser 
        915                 920                 925             


Gly Leu Asp Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Gly Arg 
    930                 935                 940                 


<210>  23
<211>  944
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - engineered PDCD-1 megaTAL

<400>  23

Met Gly Ser Cys Arg Pro Pro Lys Lys Lys Arg Lys Val Val Asp Leu 
1               5                   10                  15      


Arg Thr Leu Gly Tyr Ser Gln Gln Gln Gln Glu Lys Ile Lys Pro Lys 
            20                  25                  30          


Val Arg Ser Thr Val Ala Gln His His Glu Ala Leu Val Gly His Gly 
        35                  40                  45              


Phe Thr His Ala His Ile Val Ala Leu Ser Gln His Pro Ala Ala Leu 
    50                  55                  60                  


Gly Thr Val Ala Val Thr Tyr Gln His Ile Ile Thr Ala Leu Pro Glu 
65                  70                  75                  80  


Ala Thr His Glu Asp Ile Val Gly Val Gly Lys Gln Trp Ser Gly Ala 
                85                  90                  95      


Arg Ala Leu Glu Ala Leu Leu Thr Asp Ala Gly Glu Leu Arg Gly Pro 
            100                 105                 110         


Pro Leu Gln Leu Asp Thr Gly Gln Leu Val Lys Ile Ala Lys Arg Gly 
        115                 120                 125             


Gly Val Thr Ala Met Glu Ala Val His Ala Ser Arg Asn Ala Leu Thr 
    130                 135                 140                 


Gly Ala Pro Leu Asn Leu Thr Pro Asp Gln Val Val Ala Ile Ala Ser 
145                 150                 155                 160 


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


Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln Val Val Ala Ile 
            180                 185                 190         


Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu 
        195                 200                 205             


Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln Val Val 
    210                 215                 220                 


Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr Val Gln 
225                 230                 235                 240 


Arg Leu Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln 
                245                 250                 255     


Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr 
            260                 265                 270         


Val Gln Arg Leu Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro 
        275                 280                 285             


Asp Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu 
    290                 295                 300                 


Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Asp His Gly Leu 
305                 310                 315                 320 


Thr Pro Asp Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gln 
                325                 330                 335     


Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln Asp His 
            340                 345                 350         


Gly Leu Thr Pro Asp Gln Val Val Ala Ile Ala Ser Asn Asn Gly Gly 
        355                 360                 365             


Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu Cys Gln 
    370                 375                 380                 


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


Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu Leu Pro Val Leu 
                405                 410                 415     


Cys Gln Asp His Gly Leu Thr Pro Asp Gln Val Val Ala Ile Ala Ser 
            420                 425                 430         


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


Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln Val Val Ala Ile 
    450                 455                 460                 


Ala Ser Asn Asn Gly Gly Lys Gln Ala Leu Glu Thr Val Gln Arg Leu 
465                 470                 475                 480 


Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln Val Val 
                485                 490                 495     


Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu Glu Thr Val Gln 
            500                 505                 510         


Arg Leu Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro Asp Gln 
        515                 520                 525             


Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gln Ala Leu Glu Thr 
    530                 535                 540                 


Val Gln Arg Leu Leu Pro Val Leu Cys Gln Asp His Gly Leu Thr Pro 
545                 550                 555                 560 


Asp Gln Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gln Ala Leu 
                565                 570                 575     


Glu Ser Ile Val Ala Gln Leu Ser Arg Pro Asp Pro Ala Leu Ala Ala 
            580                 585                 590         


Leu Thr Asn Asp His Leu Val Ala Leu Ala Cys Leu Gly Gly Arg Pro 
        595                 600                 605             


Ala Met Asp Ala Val Lys Lys Gly Leu Pro His Ala Pro Glu Leu Ile 
    610                 615                 620                 


Arg Arg Val Asn Arg Arg Ile Gly Glu Arg Thr Ser His Arg Val Ala 
625                 630                 635                 640 


Ile Ser Arg Val Gly Gly Ser Ser Arg Arg Glu Ser Ile Asn Pro Trp 
                645                 650                 655     


Thr Leu Thr Gly Phe Ala Asp Ala Glu Gly Ser Phe Gly Leu Ser Ile 
            660                 665                 670         


Leu Asn Arg Asn Arg Gly Thr Ala Arg Tyr His Thr Arg Leu Ser Phe 
        675                 680                 685             


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


Ser Thr Trp Lys Val Gly Ser Ile Leu Asn Asn Gly Asp His Tyr Val 
705                 710                 715                 720 


Ser Leu Val Val Tyr Ala Phe Glu Asp Leu Lys Val Ile Ile Asp His 
                725                 730                 735     


Phe Glu Lys Tyr Pro Leu Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu 
            740                 745                 750         


Phe Lys Gln Ala Phe Ser Val Met Glu Asn Lys Glu His Leu Lys Glu 
        755                 760                 765             


Asn Gly Ile Lys Glu Leu Val Arg Ile Lys Ala Lys Met Asn Trp Gly 
    770                 775                 780                 


Leu Asn Asp Glu Leu Lys Lys Ala Phe Pro Glu Val Ile Ser Arg Glu 
785                 790                 795                 800 


Arg Pro Leu Ile Asn Lys Asn Ile Pro Asn Gly Lys Trp Leu Ala Gly 
                805                 810                 815     


Phe Thr Ser Gly Asp Gly Ser Phe Phe Val Arg Leu Arg Lys Ser Asn 
            820                 825                 830         


Val Asn Ala Arg Val Arg Val Gln Leu Val Phe Glu Ile Ser Gln His 
        835                 840                 845             


Ile Arg Asp Lys Asn Leu Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys 
    850                 855                 860                 


Gly His Ile Tyr Glu Gly Asn Lys Ser Glu Arg Ser Trp Leu Gln Phe 
865                 870                 875                 880 


Arg Val Glu Lys Phe Ser Asp Ile Asn Asp Lys Ile Ile Pro Val Phe 
                885                 890                 895     


Gln Glu Asn Thr Leu Ile Gly Met Lys Leu Glu Asp Phe Glu Asp Trp 
            900                 905                 910         


Cys Lys Val Ala Lys Leu Ile Glu Glu Lys Lys His Leu Thr Glu Ser 
        915                 920                 925             


Gly Leu Asp Glu Ile Lys Lys Ile Lys Leu Asn Met Asn Lys Arg Arg 
    930                 935                 940                 


<210>  24
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  24

Gly Gly Gly 
1           


<210>  25
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  25

Asp Gly Gly Gly Ser 
1               5   


<210>  26
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  26

Thr Gly Glu Lys Pro 
1               5   


<210>  27
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  27

Gly Gly Arg Arg 
1               


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

<220>
<223>  Exemplary linker sequence

<400>  28

Gly Gly Gly Gly Ser 
1               5   


<210>  29
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  29

Glu Gly Lys Ser Ser Gly Ser Gly Ser Glu Ser Lys Val Asp 
1               5                   10                  


<210>  30
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  30

Lys Glu Ser Gly Ser Val Ser Ser Glu Gln Leu Ala Gln Phe Arg Ser 
1               5                   10                  15      


Leu Asp 
        


<210>  31
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  31

Gly Gly Arg Arg Gly Gly Gly Ser 
1               5               


<210>  32
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  32

Leu Arg Gln Arg Asp Gly Glu Arg Pro 
1               5                   


<210>  33
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  33

Leu Arg Gln Lys Asp Gly Gly Gly Ser Glu Arg Pro 
1               5                   10          


<210>  34
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  34

Leu Arg Gln Lys Asp Gly Gly Gly Ser Gly Gly Gly Ser Glu Arg Pro 
1               5                   10                  15      


<210>  35
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cleavage sequence by TEV protease


<220>
<221>  misc_feature
<222>  (2)..(3)
<223>  Xaa is any amino acid

<220>
<221>  misc_feature
<222>  (5)..(5)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa = Gly or Ser

<400>  35

Glu Xaa Xaa Tyr Xaa Gln Xaa 
1               5           


<210>  36
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cleavage sequence by TEV protease

<400>  36

Glu Asn Leu Tyr Phe Gln Gly 
1               5           


<210>  37
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cleavage sequence by TEV protease

<400>  37

Glu Asn Leu Tyr Phe Gln Ser 
1               5           


<210>  38
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  38

Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val 
1               5                   10                  15      


Glu Glu Asn Pro Gly Pro 
            20          


<210>  39
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  39

Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn 
1               5                   10                  15      


Pro Gly Pro 
            


<210>  40
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  40

Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro 
1               5                   10                  


<210>  41
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  41

Gly Ser Gly Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu 
1               5                   10                  15      


Glu Asn Pro Gly Pro 
            20      


<210>  42
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  42

Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro 
1               5                   10                  15      


Gly Pro 
        


<210>  43
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  43

Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro Gly Pro 
1               5                   10              


<210>  44
<211>  23
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  44

Gly Ser Gly Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp 
1               5                   10                  15      


Val Glu Ser Asn Pro Gly Pro 
            20              


<210>  45
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  45

Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp Val Glu Ser 
1               5                   10                  15      


Asn Pro Gly Pro 
            20  


<210>  46
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  46

Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro 
1               5                   10                  


<210>  47
<211>  25
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  47

Gly Ser Gly Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala 
1               5                   10                  15      


Gly Asp Val Glu Ser Asn Pro Gly Pro 
            20                  25  


<210>  48
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  48

Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val 
1               5                   10                  15      


Glu Ser Asn Pro Gly Pro 
            20          


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

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  49

Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro 
1               5                   10                  


<210>  50
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  50

Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 
1               5                   10                  15      


Pro Gly Pro 
            


<210>  51
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  51

Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 
1               5                   10                  15      


Pro Gly Pro 
            


<210>  52
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  52

Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro 
1               5                   10                  


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

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  53

Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly 
1               5                   10                  15      


Pro 
    


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

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  54

Gln Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser 
1               5                   10                  15      


Asn Pro Gly Pro 
            20  


<210>  55
<211>  24
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  55

Ala Pro Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly 
1               5                   10                  15      


Asp Val Glu Ser Asn Pro Gly Pro 
            20                  


<210>  56
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  56

Val Thr Glu Leu Leu Tyr Arg Met Lys Arg Ala Glu Thr Tyr Cys Pro 
1               5                   10                  15      


Arg Pro Leu Leu Ala Ile His Pro Thr Glu Ala Arg His Lys Gln Lys 
            20                  25                  30          


Ile Val Ala Pro Val Lys Gln Thr 
        35                  40  


<210>  57
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  57

Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro 
1               5                   10                  15      


Gly Pro 
        


<210>  58
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  58

Leu Leu Ala Ile His Pro Thr Glu Ala Arg His Lys Gln Lys Ile Val 
1               5                   10                  15      


Ala Pro Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly 
            20                  25                  30          


Asp Val Glu Ser Asn Pro Gly Pro 
        35                  40  


<210>  59
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Self-cleaving polypeptide comprising 2A site

<400>  59

Glu Ala Arg His Lys Gln Lys Ile Val Ala Pro Val Lys Gln Thr Leu 
1               5                   10                  15      


Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly 
            20                  25                  30          


Pro 
    


