                         SEQUENCE LISTING

<110>  bluebird bio, Inc.
       Jarjour, Jordan
       Havens, Kyle
 
<120>  TGFBetaR2 ENDONUCLEASE VARIANTS, COMPOSITIONS, AND METHODS OF USE

<130>  BLBD-078/02WO

<150>  US 62/414,260
<151>  2016-10-28

<150>  US 62/409,163
<151>  2016-10-17

<160>  66    

<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 subsp. americana (mitochondrion)


<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>  303
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized I-OnuI variant


<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>  6

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 Met Leu Arg Ile Arg Asn Arg 
            20                  25                  30          


Asn Gln Arg Lys Ala Asn Tyr Gly Thr Ser Leu Val Phe Glu Ile Gly 
        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 Arg Asn Ser Gly Asp Gly Ser Val Arg Leu Ser 
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 Leu 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 Leu Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Gly Val Asp Leu Ile Lys Arg Lys Arg Lys Thr 
            180                 185                 190         


Thr Val Gly Val Gly Leu Arg Phe Ser Ile Ser 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                 


Tyr Glu Arg Asn Lys Ser Glu Asn Ser Trp Leu Asp Phe Val Val Arg 
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>  7
<211>  303
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized I-OnuI variant


<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>  7

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 Met Leu Arg Ile Arg Asn Arg 
            20                  25                  30          


Asn Gln Arg Lys Ala Asn Tyr Gly Thr Ser Leu Val Phe Glu Ile Gly 
        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 Arg Asn Ser Gly Asp Gly Ser Val Arg Leu Ser 
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 Leu 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 Leu Lys Trp Leu Ala Gly Phe Thr Ser 
                165                 170                 175     


Gly Asp Gly Ser Phe Gly Val Asp Leu Ile Lys Arg Lys Arg Lys Thr 
            180                 185                 190         


Thr Val Gly Val Gly Leu Arg Phe Ser 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 Arg Asn Lys Ser Glu Asn Ser Trp Leu Asp Phe Val Val Arg 
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 Lys 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>  8
<211>  874
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized megaTAL TGFbR2.B3 construct

<400>  8

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Gln Leu Ser Arg Pro Asp Pro Ala Leu Ala Ala Leu Thr Asn Asp His 
        515                 520                 525             


Leu Val Ala Leu Ala Cys Leu Gly Gly Arg Pro Ala Met Asp Ala Val 
    530                 535                 540                 


Lys Lys Gly Leu Pro His Ala Pro Glu Leu Ile Arg Arg Val Asn Arg 
545                 550                 555                 560 


Arg Ile Gly Glu Arg Thr Ser His Arg Val Ala Ile Ser Arg Val Gly 
                565                 570                 575     


Gly Ser Arg Arg Glu Ser Ile Asn Pro Trp Ile Leu Thr Gly Phe Ala 
            580                 585                 590         


Asp Ala Glu Gly Ser Phe Met Leu Arg Ile Arg Asn Arg Asn Gln Arg 
        595                 600                 605             


Lys Ala Asn Tyr Gly Thr Ser Leu Val Phe Glu Ile Gly Leu His Asn 
    610                 615                 620                 


Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp Lys Val Gly 
625                 630                 635                 640 


Lys Ile Arg Asn Ser Gly Asp Gly Ser Val Arg Leu Ser Val Thr Arg 
                645                 650                 655     


Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys Tyr Pro Leu 
            660                 665                 670         


Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln Ala Phe Ser 
        675                 680                 685             


Leu Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile Lys Glu Leu 
    690                 695                 700                 


Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp Glu Leu Lys 
705                 710                 715                 720 


Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Pro Leu Ile Asn Lys 
                725                 730                 735     


Asn Ile Pro Asn Leu Lys Trp Leu Ala Gly Phe Thr Ser Gly Asp Gly 
            740                 745                 750         


Ser Phe Gly Val Asp Leu Ile Lys Arg Lys Arg Lys Thr Thr Val Gly 
        755                 760                 765             


Val Gly Leu Arg Phe Ser Ile Ser Gln His Ile Arg Asp Lys Asn Leu 
    770                 775                 780                 


Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly Arg Ile Tyr Glu Arg 
785                 790                 795                 800 


Asn Lys Ser Glu Asn Ser Trp Leu Asp Phe Val Val Arg Lys Phe Ser 
                805                 810                 815     


Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn Thr Leu Ile 
            820                 825                 830         


Gly Val Lys Leu Glu Asp Phe Glu Asp Trp Cys Lys Val Ala Lys Leu 
        835                 840                 845             


Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp Glu Ile Lys 
    850                 855                 860                 


Lys Ile Lys Leu Asn Met Asn Lys Gly Arg 
865                 870                 


<210>  9
<211>  874
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized megaTAL TGFbR2.B3.F8 construct

<400>  9

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Gln Leu Ser Arg Pro Asp Pro Ala Leu Ala Ala Leu Thr Asn Asp His 
        515                 520                 525             


Leu Val Ala Leu Ala Cys Leu Gly Gly Arg Pro Ala Met Asp Ala Val 
    530                 535                 540                 


Lys Lys Gly Leu Pro His Ala Pro Glu Leu Ile Arg Arg Val Asn Arg 
545                 550                 555                 560 


Arg Ile Gly Glu Arg Thr Ser His Arg Val Ala Ile Ser Arg Val Gly 
                565                 570                 575     


Gly Ser Arg Arg Glu Ser Ile Asn Pro Trp Ile Leu Thr Gly Phe Ala 
            580                 585                 590         


Asp Ala Glu Gly Ser Phe Met Leu Arg Ile Arg Asn Arg Asn Gln Arg 
        595                 600                 605             


Lys Ala Asn Tyr Gly Thr Ser Leu Val Phe Glu Ile Gly Leu His Asn 
    610                 615                 620                 


Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp Lys Val Gly 
625                 630                 635                 640 


Lys Ile Arg Asn Ser Gly Asp Gly Ser Val Arg Leu Ser Val Thr Arg 
                645                 650                 655     


Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys Tyr Pro Leu 
            660                 665                 670         


Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln Ala Phe Ser 
        675                 680                 685             


Leu Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile Lys Glu Leu 
    690                 695                 700                 


Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp Glu Leu Lys 
705                 710                 715                 720 


Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Pro Leu Ile Asn Lys 
                725                 730                 735     


Asn Ile Pro Asn Leu Lys Trp Leu Ala Gly Phe Thr Ser Gly Asp Gly 
            740                 745                 750         


Ser Phe Gly Val Asp Leu Ile Lys Arg Lys Arg Lys Thr Thr Val Gly 
        755                 760                 765             


Val Gly Leu Arg Phe Ser Ile Ser Gln His Ile Arg Asp Lys Asn Leu 
    770                 775                 780                 


Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly His Ile Tyr Glu Arg 
785                 790                 795                 800 


Asn Lys Ser Glu Asn Ser Trp Leu Asp Phe Val Val Arg Lys Phe Ser 
                805                 810                 815     


Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn Thr Leu Ile 
            820                 825                 830         


Gly Val Lys Leu Lys Asp Phe Glu Asp Trp Cys Lys Val Ala Lys Leu 
        835                 840                 845             


Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp Glu Ile Lys 
    850                 855                 860                 


Lys Ile Lys Leu Asn Met Asn Lys Gly Arg 
865                 870                 


<210>  10
<211>  1115
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized megaTAL TGFbR2.B3.F8 - Trex2 fusion protein

<400>  10

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Gln Leu Ser Arg Pro Asp Pro Ala Leu Ala Ala Leu Thr Asn Asp His 
        515                 520                 525             


Leu Val Ala Leu Ala Cys Leu Gly Gly Arg Pro Ala Met Asp Ala Val 
    530                 535                 540                 


Lys Lys Gly Leu Pro His Ala Pro Glu Leu Ile Arg Arg Val Asn Arg 
545                 550                 555                 560 


Arg Ile Gly Glu Arg Thr Ser His Arg Val Ala Ile Ser Arg Val Gly 
                565                 570                 575     


Gly Ser Arg Arg Glu Ser Ile Asn Pro Trp Ile Leu Thr Gly Phe Ala 
            580                 585                 590         


Asp Ala Glu Gly Ser Phe Met Leu Arg Ile Arg Asn Arg Asn Gln Arg 
        595                 600                 605             


Lys Ala Asn Tyr Gly Thr Ser Leu Val Phe Glu Ile Gly Leu His Asn 
    610                 615                 620                 


Lys Asp Lys Ser Ile Leu Glu Asn Ile Gln Ser Thr Trp Lys Val Gly 
625                 630                 635                 640 


Lys Ile Arg Asn Ser Gly Asp Gly Ser Val Arg Leu Ser Val Thr Arg 
                645                 650                 655     


Phe Glu Asp Leu Lys Val Ile Ile Asp His Phe Glu Lys Tyr Pro Leu 
            660                 665                 670         


Ile Thr Gln Lys Leu Gly Asp Tyr Lys Leu Phe Lys Gln Ala Phe Ser 
        675                 680                 685             


Leu Met Glu Asn Lys Glu His Leu Lys Glu Asn Gly Ile Lys Glu Leu 
    690                 695                 700                 


Val Arg Ile Lys Ala Lys Met Asn Trp Gly Leu Asn Asp Glu Leu Lys 
705                 710                 715                 720 


Lys Ala Phe Pro Glu Asn Ile Ser Lys Glu Arg Pro Leu Ile Asn Lys 
                725                 730                 735     


Asn Ile Pro Asn Leu Lys Trp Leu Ala Gly Phe Thr Ser Gly Asp Gly 
            740                 745                 750         


Ser Phe Gly Val Asp Leu Ile Lys Arg Lys Arg Lys Thr Thr Val Gly 
        755                 760                 765             


Val Gly Leu Arg Phe Ser Ile Ser Gln His Ile Arg Asp Lys Asn Leu 
    770                 775                 780                 


Met Asn Ser Leu Ile Thr Tyr Leu Gly Cys Gly His Ile Tyr Glu Arg 
785                 790                 795                 800 


Asn Lys Ser Glu Asn Ser Trp Leu Asp Phe Val Val Arg Lys Phe Ser 
                805                 810                 815     


Asp Ile Asn Asp Lys Ile Ile Pro Val Phe Gln Glu Asn Thr Leu Ile 
            820                 825                 830         


Gly Val Lys Leu Lys Asp Phe Glu Asp Trp Cys Lys Val Ala Lys Leu 
        835                 840                 845             


Ile Glu Glu Lys Lys His Leu Thr Glu Ser Gly Leu Asp Glu Ile Lys 
    850                 855                 860                 


Lys Ile Lys Leu Asn Met Asn Lys Gly Arg Val Phe Ala Ser Thr Gly 
865                 870                 875                 880 


Ser Glu Pro Pro Arg Ala Glu Thr Phe Val Phe Leu Asp Leu Glu Ala 
                885                 890                 895     


Thr Gly Leu Pro Asn Met Asp Pro Glu Ile Ala Glu Ile Ser Leu Phe 
            900                 905                 910         


Ala Val His Arg Ser Ser Leu Glu Asn Pro Glu Arg Asp Asp Ser Gly 
        915                 920                 925             


Ser Leu Val Leu Pro Arg Val Leu Asp Lys Leu Thr Leu Cys Met Cys 
    930                 935                 940                 


Pro Glu Arg Pro Phe Thr Ala Lys Ala Ser Glu Ile Thr Gly Leu Ser 
945                 950                 955                 960 


Ser Glu Ser Leu Met His Cys Gly Lys Ala Gly Phe Asn Gly Ala Val 
                965                 970                 975     


Val Arg Thr Leu Gln Gly Phe Leu Ser Arg Gln Glu Gly Pro Ile Cys 
            980                 985                 990         


Leu Val Ala His Asn Gly Phe Asp  Tyr Asp Phe Pro Leu  Leu Cys Thr 
        995                 1000                 1005             


Gly Leu  Gln Arg Leu Gly Ala  His Leu Pro Gln Asp  Thr Val Cys 
    1010                 1015                 1020             


Leu Asp  Thr Leu Pro Ala Leu  Arg Gly Leu Asp Arg  Ala His Ser 
    1025                 1030                 1035             


His Gly  Thr Arg Ala Gln Gly  Arg Lys Ser Tyr Ser  Leu Ala Ser 
    1040                 1045                 1050             


Leu Phe  His Arg Tyr Phe Gln  Ala Glu Pro Ser Ala  Ala His Ser 
    1055                 1060                 1065             


Ala Glu  Gly Asp Val His Thr  Leu Leu Leu Ile Phe  Leu His Arg 
    1070                 1075                 1080             


Ala Pro  Glu Leu Leu Ala Trp  Ala Asp Glu Gln Ala  Arg Ser Trp 
    1085                 1090                 1095             


Ala His  Ile Glu Pro Met Tyr  Val Pro Pro Asp Gly  Pro Ser Leu 
    1100                 1105                 1110             


Glu Ala  
    1115 


<210>  11
<211>  22
<212>  DNA
<213>  Homo sapiens

<400>  11
cgaccagaaa ttcccagctt ct                                                22


<210>  12
<211>  11
<212>  DNA
<213>  Homo sapiens

<400>  12
gttgagagat c                                                            11


<210>  13
<211>  38
<212>  DNA
<213>  Homo sapiens

<400>  13
gttgagagat cgagggcgac cagaaattcc cagcttct                               38


<210>  14
<211>  22
<212>  DNA
<213>  Homo sapiens

<400>  14
cgaccagaaa ttcaaccttt ta                                                22


<210>  15
<211>  22
<212>  DNA
<213>  Homo sapiens

<400>  15
cgaccagaaa ttctacgtct gc                                                22


<210>  16
<211>  22
<212>  DNA
<213>  Homo sapiens

<400>  16
cgaccagaaa ttccacaggc tc                                                22


<210>  17
<211>  22
<212>  DNA
<213>  Homo sapiens

<400>  17
cgaccagaaa ttcaccgatt tt                                                22


<210>  18
<211>  22
<212>  DNA
<213>  Homo sapiens

<400>  18
cttccaggaa ttcccagctt ct                                                22


<210>  19
<211>  7244
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthesized I-OnuI variant TGFbR2.B3.F8 surface display plasmid 
       construct

<400>  19
gacgaaaggg cctcgtgata cgcctatttt tataggttaa tgtcatgata ataatggttt       60

cttaggacgg atcgcttgcc tgtaacttac acgcgcctcg tatcttttaa tgatggaata      120

atttgggaat ttactctgtg tttatttatt tttatgtttt gtatttggat tttagaaagt      180

aaataaagaa ggtagaagag ttacggaatg aagaaaaaaa aataaacaaa ggtttaaaaa      240

atttcaacaa aaagcgtact ttacatatat atttattaga caagaaaagc agattaaata      300

gatatacatt cgattaacga taagtaaaat gtaaaatcac aggattttcg tgtgtggtct      360

tctacacaga caagatgaaa caattcggca ttaatacctg agagcaggaa gagcaagata      420

aaaggtagta tttgttggcg atccccctag agtcttttac atcttcggaa aacaaaaact      480

attttttctt taatttcttt ttttactttc tatttttaat ttatatattt atattaaaaa      540

atttaaatta taattatttt tatagcacgt gatgaaaagg acccaggtgg cacttttcgg      600

ggaaatgtgc gcggaacccc tatttgttta tttttctaaa tacattcaaa tatgtatccg      660

ctcatgagac aataaccctg ataaatgctt caataatatt gaaaaaggaa gagtatgagt      720

attcaacatt tccgtgtcgc ccttattccc ttttttgcgg cattttgcct tcctgttttt      780

gctcacccag aaacgctggt gaaagtaaaa gatgctgaag atcagttggg tgcacgagtg      840

ggttacatcg aactggatct caacagcggt aagatccttg agagttttcg ccccgaagaa      900

cgttttccaa tgatgagcac ttttaaagtt ctgctatgtg gcgcggtatt atcccgtatt      960

gacgccgggc aagagcaact cggtcgccgc atacactatt ctcagaatga cttggttgag     1020

tactcaccag tcacagaaaa gcatcttacg gatggcatga cagtaagaga attatgcagt     1080

gctgccataa ccatgagtga taacactgcg gccaacttac ttctgacaac gatcggagga     1140

ccgaaggagc taaccgcttt ttttcacaac atgggggatc atgtaactcg ccttgatcgt     1200

tgggaaccgg agctgaatga agccatacca aacgacgagc gtgacaccac gatgcctgta     1260

gcaatggcaa caacgttgcg caaactatta actggcgaac tacttactct agcttcccgg     1320

caacaattaa tagactggat ggaggcggat aaagttgcag gaccacttct gcgctcggcc     1380

cttccggctg gctggtttat tgctgataaa tctggagccg gtgagcgtgg gtctcgcggt     1440

atcattgcag cactggggcc agatggtaag ccctcccgta tcgtagttat ctacacgacg     1500

ggcagtcagg caactatgga tgaacgaaat agacagatcg ctgagatagg tgcctcactg     1560

attaagcatt ggtaactgtc agaccaagtt tactcatata tactttagat tgatttaaaa     1620

cttcattttt aatttaaaag gatctaggtg aagatccttt ttgataatct catgaccaaa     1680

atcccttaac gtgagttttc gttccactga gcgtcagacc ccgtagaaaa gatcaaagga     1740

tcttcttgag atcctttttt tctgcgcgta atctgctgct tgcaaacaaa aaaaccaccg     1800

ctaccagcgg tggtttgttt gccggatcaa gagctaccaa ctctttttcc gaaggtaact     1860

ggcttcagca gagcgcagat accaaatact gtccttctag tgtagccgta gttaggccac     1920

cacttcaaga actctgtagc accgcctaca tacctcgctc tgctaatcct gttaccagtg     1980

gctgctgcca gtggcgataa gtcgtgtctt accgggttgg actcaagacg atagttaccg     2040

gataaggcgc agcggtcggg ctgaacgggg ggttcgtgca cacagcccag cttggagcga     2100

acgacctaca ccgaactgag atacctacag cgtgagcatt gagaaagcgc cacgcttccc     2160

gaagggagaa aggcggacag gtatccggta agcggcaggg tcggaacagg agagcgcacg     2220

agggagcttc caggggggaa cgcctggtat ctttatagtc ctgtcgggtt tcgccacctc     2280

tgacttgagc gtcgattttt gtgatgctcg tcaggggggc cgagcctatg gaaaaacgcc     2340

agcaacgcgg cctttttacg gttcctggcc ttttgctggc cttttgctca catgttcttt     2400

cctgcgttat cccctgattc tgtggataac cgtattaccg cctttgagtg agctgatacc     2460

gctcgccgca gccgaacgac cgagcgcagc gagtcagtga gcgaggaagc ggaagagcgc     2520

ccaatacgca aaccgcctct ccccgcgcgt tggccgattc attaatgcag ctggcacgac     2580

aggtttcccg actggaaagc gggcagtgag cgcaacgcaa ttaatgtgag ttacctcact     2640

cattaggcac cccaggcttt acactttatg cttccggctc ctatgttgtg tggaattgtg     2700

agcggataac aatttcacac aggaaacagc tatgaccatg attacgccaa gctcggaatt     2760

aaccctcact aaagggaaca aaagctgggt acccgacagg ttatcagcaa caacacagtc     2820

atatccattc tcaattagct ctaccacagt gtgtgaacca atgtatccag caccacctgt     2880

aaccaaaaca attttagaag tactttcact ttgtaactga gctgtcattt atattgaatt     2940

ttcaaaaatt cttacttttt ttttggatgg acgcaaagaa gtttaataat catattacat     3000

ggcattacca ccatatacat atccatatac atatccatat ctaatcttac ttatatgttg     3060

tggaaatgta aagagcccca ttatcttagc ctaaaaaaac cttctctttg gaactttcag     3120

taatacgctt aactgctcat tgctatattg aagtacggat tagaagccgc cgagcgggtg     3180

acagccctcc gaaggaagac tctcctccgt gcgtcctcgt cttcaccggt cgcgttcctg     3240

aaacgcagat gtgcctcgcg ccgcactgct ccgaacaata aagattctac aatactagct     3300

tttatggtta tgaagaggaa aaattggcag taacctggcc ccacaaacct tcaaatgaac     3360

gaatcaaatt aacaaccata ggatgataat gcgattagtt ttttagcctt atttctgggg     3420

taattaatca gcgaagcgat gatttttgat ctattaacag atatataaat gcaaaaactg     3480

cataaccact ttaactaata ctttcaacat tttcggtttg tattacttct tattcaaatg     3540

taataaaaga tcgaatccta cttcatacat tttcaattaa gatgcagtta cttcgctgtt     3600

tttcaatatt ttctgttatt gcttcagttt tagcacagga actgacaact atatgcgagc     3660

aaatcccctc accaacttta gaatcgacgc cgtactcttt gtcaacgact actattttgg     3720

ccaacgggaa ggcaatgcaa ggagtttttg aatattacaa atcagtaacg tttgtcagta     3780

attgcggttc tcacccctca acaactagca aaggcagccc cataaacaca cagtatgttt     3840

ttaaggacaa tagctcgacg attgaaggta gatacccata cgacgttcca gactacgctc     3900

tgcaggctag tggtggagga ggctctggtg gaggcggtag cggaggcgga gggtcggcta     3960

gctccatcaa cccatggatt ctgactggtt tcgctgatgc cgaaggatcc ttcatgctac     4020

gtatcaggaa cagaaaccaa aggaaagcta attacggaac tagcctggta ttcgaaatcg     4080

gactgcacaa caaggacaaa tcgattctgg agaatatcca gtcgacttgg aaggtcggca     4140

aaatcaggaa cagtggcgac ggtagtgtca gactgagtgt cacacgtttc gaagatttga     4200

aagtgattat cgaccacttc gagaaatatc cgctgattac ccagaaattg ggcgattaca     4260

agttgtttaa acaggcattc agcctcatgg agaacaaaga acatcttaag gagaatggga     4320

ttaaggagct cgtacgaatc aaagctaaga tgaattgggg tctcaatgac gaattgaaaa     4380

aagcatttcc agagaacatt agcaaagagc gtccccttat caataagaac atcccaaatc     4440

tcaaatggct ggctggattc acatctggtg acggctcgtt cggagtggat ctaatcaaga     4500

ggaaaagaaa aactacagta ggagtgggcc tgcgattctc catctcacag cacatcagag     4560

acaagaacct gatgaattca ttgataacat acctaggctg tggtcacatc tacgagagaa     4620

acaagtctga gaatagttgg ctcgatttcg ttgtaagaaa attcagcgat atcaacgaca     4680

agatcattcc ggtattccag gaaaatactc tgattggcgt caaactcaag gactttgaag     4740

attggtgcaa ggttgccaaa ttgatcgaag agaagaaaca cctgaccgaa tccggtttgg     4800

atgagattaa gaaaatcaag ctgaacatga acaaaggtcg tgtcttctct agaggcggtt     4860

ccagaagcgg atctggtact ggcgaacaga aactcataag cgaagaagac cttagcggga     4920

ctggagagca aaagttgatt tctgaggagg atttgtcggg aaccggggag cagaagttaa     4980

tcagtgaaga ggatctcagt ggaacgggcg aacaaaagtt gatctcggag gaagacttat     5040

aatgaagatc tgataacaac agtgtagatg taacaaaatc gactttgttc ccactgtact     5100

tttagctcgt acaaaataca atatactttt catttctccg taaacaacat gttttcccat     5160

gtaatatcct tttctatttt tcgttccgtt accaacttta cacatacttt atatagctat     5220

tcacttctat acactaaaaa actaagacaa ttttaatttt gctgcctgcc atatttcaat     5280

ttgttataaa ttcctataat ttatcctatt agtagctaaa aaaagatgaa tgtgaatcga     5340

atcctaagag aattgagctc caattcgccc tatagtgagt cgtattacaa ttcactggcc     5400

gtcgttttac aacgtcgtga ctgggaaaac cctggcgtta cccaacttaa tcgccttgca     5460

gcacatcccc ctttcgccag ctggcgtaat agcgaagagg cccgcaccga tcgcctttcc     5520

caacagttgc gcagcctgaa tggcgaatgg acgcgccctg tagcggcgca ttaagcgcgg     5580

cgggtgtggt ggttacgcgc agcgtgaccg ctacacttgc cagcgcccta gcgcccgctc     5640

ctttcgcttt cttcccttcc tttctcgcca cgttcgccgg ctttccccgt caagctctaa     5700

atcgggggct ccctttaggg ttccgattta gtgctttacg gcacctcgac cccaaaaaac     5760

ttgattaggg tgatggttca cgtagtgggc catcgccctg atagacggtt tttcgccctt     5820

tgacgttgga gtccacgttc tttaatagtg gactcttgtt ccaaactgga acaacactca     5880

accctatctc ggtctattct tttgatttat aagggatttt gccgatttcg gcctattggt     5940

taaaaaatga gctgatttaa caaaaattta acgcgaattt taacaaaata ttaacgttta     6000

caatttcctg atgcggtatt ttctccttac gcatctgtgc ggtatttcac accgcaggca     6060

agtgcacaaa caatacttaa ataaatacta ctcagtaata acctatttct tagcattttt     6120

gacgaaattt gctattttgt tagagtcttt tacaccattt gtctccacac ctccgcttac     6180

atcaacacca ataacgccat ttaatctaag cgcatcacca acattttctg gcgtcagtcc     6240

accagctaac ataaaatgta agctttcggg gctctcttgc cttccaaccc agtcagaaat     6300

cgagttccaa tccaaaagtt cacctgtccc acctgcttct gaatcaaaca agggaataaa     6360

cgaatgaggt ttctgtgaag ctgcactgag tagtatgttg cagtcttttg gaaatacgag     6420

tcttttaata actggcaaac cgaggaactc ttggtattct tgccacgact catctccatg     6480

cagttggacg acatcaatgc cgtaatcatt gaccagagcc aaaacatcct ccttaggttg     6540

attacgaaac acgccaacca agtatttcgg agtgcctgaa ctatttttat atgcttttac     6600

aagacttgaa attttccttg caataaccgg gtcaattgtt ctctttctat tgggcacaca     6660

tataataccc agcaagtcag catcggaatc aagagcacat tctgcggcct ctgtgctctg     6720

caagccgcaa actttcacca atggaccaga actacctgtg aaattaataa cagacatact     6780

ccaagctgcc tttgtgtgct taatcacgta tactcacgtg ctcaatagtc accaatgccc     6840

tccctcttgg ccctctcctt ttcttttttc gaccgaatta attcttaatc ggcaaaaaaa     6900

gaaaagctcc ggatcaagat tgtacgtaag gtgacaagct atttttcaat aaagaatatc     6960

ttccactact gccatctggc gtcataactg caaagtacac atatattacg atgctgtcta     7020

ttaaatgctt cctatattat atatatagta atgtcgttta tggtgcactc tcagtacaat     7080

ctgctctgat gccgcatagt taagccagcc ccgacacccg ccaacacccg ctgacgcgcc     7140

ctgacgggct tgtctgctcc cggcatccgc ttacagacaa gctgtgaccg tctccgggag     7200

ctgcatgtgt cagaggtttt caccgtcatc accgaaacgc gcga                      7244


<210>  20
<211>  2640
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthesized megaTAL TGFbR2.B3.F8 construct

<400>  20
augggauccg cgccaccuaa gaagaaacgc aaagucgugg aucuacgcac gcucggcuac       60

agucagcagc agcaagagaa gaucaaaccg aaggugcguu cgacaguggc gcagcaccac      120

gaggcacugg ugggccaugg guuuacacac gcgcacaucg uugcgcucag ccaacacccg      180

gcagcguuag ggaccgucgc ugucacguau cagcacauaa ucacggcguu gccagaggcg      240

acacacgaag acaucguugg cgucggcaaa cagugguccg gcgcacgcgc ccuggaggcc      300

uugcucacgg augcggggga guugagaggu ccgccguuac aguuggacac aggccaacuu      360

gugaagauug caaaacgugg cggcgugacc gcaauggagg cagugcaugc aucgcgcaau      420

gcacugacgg gugccccccu gaacuuaaca cccgaucaag ugguagcgau agcgucaaac      480

aacgggggua aacaggcuuu ggagacggua cagcgguuau ugccgguacu cugccaggac      540

cacggauuga caccggacca agugguggcg auugcgucca auggcggagg caagcaggca      600

cuagagaccg uccaacggcu ucuucccguu cuuugucagg aucaugggcu aaccccugau      660

cagguagucg cuauagcuuc aaacggcggg ggcaagcaag cacuggagac cguucaacga      720

cuccugccag ugcugugcca agaccacgga cuuaccccag aucaggucgu ugcuauugcc      780

uccaacaaug gcgggaaaca agcguuggaa acugugcaga gacuguuacc ugucuugugu      840

caagaccacg gccucacgcc agaucaggug guagccauag cgucgaacau uggugguaag      900

caagcccuug aaacggucca gcgucuucug ccgguguugu gccaggacca cggacuaacg      960

ccggaucagg ucguagccau ugcuucaaau aauggcggca aacaggcgcu agagacaguc     1020

cagcgccucu ugccuguguu augccaggau cacggcuuaa ccccagacca aguuguggcu     1080

auugcaucua auaucggugg caaacaagcc uuggagacag ugcaacgauu acugccuguc     1140

uuaugucagg aucauggccu gacgcccgau cagguagugg caaucgcauc uaacaaugga     1200

gguaagcaag cacuggagac uguccagaga uuguuacccg uacuauguca agaucauggu     1260

uugacgccug aucagguugu ugcgauagcc agcaauauag gagggaaaca ggcucuugaa     1320

accguacagc gacuucuccc agucuugugc caagaucacg ggcuuacucc ugaucaaguc     1380

guagcuaucg ccagcaaugg aggugggaaa caggcccugg aaaccguaca acgucuccuc     1440

ccaguacuuu gucaagacca cgggcugaca ccugaccaag uuguggcgau agccagucau     1500

gaugggggaa aacaggcacu agagagcauu guggcccagc ugagccggcc ugauccggcg     1560

uuggccgcgu ugaccaacga ccaccucguc gccuuggccu gccucggcgg acguccugcc     1620

auggaugcag ugaaaaaggg auugccgcac gcgccggaau ugaucagaag agucaaucgc     1680

cguauuggcg aacgcacguc ccaucgcguu gcgauaucua gagugggagg aucgcgcaga     1740

gaguccauca acccauggau ucugacuggu uucgcugaug ccgaaggauc cuucaugcua     1800

cguaucagga acagaaacca aaggaaagcu aauuacggaa cuagccuggu auucgaaauc     1860

ggacugcaca acaaggacaa aucgauucug gagaauaucc agucgacuug gaaggucggc     1920

aaaaucagga acaguggcga cgguaguguc agacugagug ucacacguuu cgaagauuug     1980

aaagugauua ucgaccacuu cgagaaauau ccgcugauua cccagaaauu gggcgauuac     2040

aaguuguuua aacaggcauu cagccucaug gagaacaaag aacaucuuaa ggagaauggg     2100

auuaaggagc ucguacgaau caaagcuaag augaauuggg gucucaauga cgaauugaaa     2160

aaagcauuuc cagagaacau uagcaaagag cguccccuua ucaauaagaa caucccaaau     2220

cucaaauggc uggcuggauu cacaucuggu gacggcucgu ucggagugga ucuaaucaag     2280

aggaaaagaa aaacuacagu aggagugggc cugcgauucu ccaucucaca gcacaucaga     2340

gacaagaacc ugaugaauuc auugauaaca uaccuaggcu guggucacau cuacgagaga     2400

aacaagucug agaauaguug gcucgauuuc guuguaagaa aauucagcga uaucaacgac     2460

aagaucauuc cgguauucca ggaaaauacu cugauuggcg ucaaacucaa ggacuuugaa     2520

gauuggugca agguugccaa auugaucgaa gagaagaaac accugaccga auccgguuug     2580

gaugagauua agaaaaucaa gcugaacaug aacaaagguc gugucuucag cggccgcuga     2640


<210>  21
<211>  711
<212>  RNA
<213>  Mus musculus

<400>  21
augucugagc caccucgggc ugagaccuuu guauuccugg accuagaagc cacugggcuc       60

ccaaacaugg acccugagau ugcagagaua ucccuuuuug cuguucaccg cucuucccug      120

gagaacccag aacgggauga uucugguucc uuggugcugc cccguguucu ggacaagcuc      180

acacugugca ugugcccgga gcgccccuuu acugccaagg ccagugagau uacugguuug      240

agcagcgaaa gccugaugca cugcgggaag gcugguuuca auggcgcugu gguaaggaca      300

cugcagggcu uccuaagccg ccaggagggc cccaucugcc uuguggccca caauggcuuc      360

gauuaugacu ucccacugcu gugcacggag cuacaacguc ugggugccca ucugccccaa      420

gacacugucu gccuggacac acugccugca uugcggggcc uggaccgugc ucacagccac      480

ggcaccaggg cucaaggccg caaaagcuac agccuggcca gucucuucca ccgcuacuuc      540

caggcugaac ccagugcugc ccauucagca gaaggugaug ugcacacccu gcuucugauc      600

uuccugcauc gugcuccuga gcugcucgcc ugggcagaug agcaggcccg cagcugggcu      660

cauauugagc ccauguacgu gccaccugau gguccaagcc ucgaagccug a               711


<210>  22
<211>  236
<212>  PRT
<213>  Mus musculus

<400>  22

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


Ala Thr Gly Leu Pro Asn Met Asp Pro Glu Ile Ala Glu Ile Ser Leu 
            20                  25                  30          


Phe Ala Val His Arg Ser Ser Leu Glu Asn Pro Glu Arg Asp Asp Ser 
        35                  40                  45              


Gly Ser Leu Val Leu Pro Arg Val Leu Asp Lys Leu Thr Leu Cys Met 
    50                  55                  60                  


Cys Pro Glu Arg Pro Phe Thr Ala Lys Ala Ser Glu Ile Thr Gly Leu 
65                  70                  75                  80  


Ser Ser Glu Ser Leu Met His Cys Gly Lys Ala Gly Phe Asn Gly Ala 
                85                  90                  95      


Val Val Arg Thr Leu Gln Gly Phe Leu Ser Arg Gln Glu Gly Pro Ile 
            100                 105                 110         


Cys Leu Val Ala His Asn Gly Phe Asp Tyr Asp Phe Pro Leu Leu Cys 
        115                 120                 125             


Thr Glu Leu Gln Arg Leu Gly Ala His Leu Pro Gln Asp Thr Val Cys 
    130                 135                 140                 


Leu Asp Thr Leu Pro Ala Leu Arg Gly Leu Asp Arg Ala His Ser His 
145                 150                 155                 160 


Gly Thr Arg Ala Gln Gly Arg Lys Ser Tyr Ser Leu Ala Ser Leu Phe 
                165                 170                 175     


His Arg Tyr Phe Gln Ala Glu Pro Ser Ala Ala His Ser Ala Glu Gly 
            180                 185                 190         


Asp Val His Thr Leu Leu Leu Ile Phe Leu His Arg Ala Pro Glu Leu 
        195                 200                 205             


Leu Ala Trp Ala Asp Glu Gln Ala Arg Ser Trp Ala His Ile Glu Pro 
    210                 215                 220                 


Met Tyr Val Pro Pro Asp Gly Pro Ser Leu Glu Ala 
225                 230                 235     


<210>  23
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  23

Gly Gly Gly 
1           


<210>  24
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  24

Asp Gly Gly Gly Ser 
1               5   


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

<220>
<223>  Exemplary linker sequence

<400>  25

Thr Gly Glu Lys Pro 
1               5   


<210>  26
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  26

Gly Gly Arg Arg 
1               


<210>  27
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  27

Gly Gly Gly Gly Ser 
1               5   


<210>  28
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  28

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


<210>  29
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  29

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


Leu Asp 
        


<210>  30
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  30

Gly Gly Arg Arg Gly Gly Gly Ser 
1               5               


<210>  31
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  31

Leu Arg Gln Arg Asp Gly Glu Arg Pro 
1               5                   


<210>  32
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  32

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


<210>  33
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Exemplary linker sequence

<400>  33

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


<210>  34
<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>  34

Glu Xaa Xaa Tyr Xaa Gln Xaa 
1               5           


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

<220>
<223>  Cleavage sequence by TEV protease

<400>  35

Glu Asn Leu Tyr Phe Gln Gly 
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 Ser 
1               5           


<210>  37
<211>  22
<212>  PRT
<213>  Artificial Sequence

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

<400>  37

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>  38
<211>  19
<212>  PRT
<213>  Artificial Sequence

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

<400>  38

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


Pro Gly Pro 
            


<210>  39
<211>  14
<212>  PRT
<213>  Artificial Sequence

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

<400>  39

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


<210>  40
<211>  21
<212>  PRT
<213>  Artificial Sequence

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

<400>  40

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>  41
<211>  18
<212>  PRT
<213>  Artificial Sequence

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

<400>  41

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


Gly Pro 
        


<210>  42
<211>  13
<212>  PRT
<213>  Artificial Sequence

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

<400>  42

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


<210>  43
<211>  23
<212>  PRT
<213>  Artificial Sequence

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

<400>  43

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>  44
<211>  20
<212>  PRT
<213>  Artificial Sequence

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

<400>  44

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>  45
<211>  14
<212>  PRT
<213>  Artificial Sequence

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

<400>  45

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


<210>  46
<211>  25
<212>  PRT
<213>  Artificial Sequence

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

<400>  46

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>  47
<211>  22
<212>  PRT
<213>  Artificial Sequence

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

<400>  47

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>  48
<211>  14
<212>  PRT
<213>  Artificial Sequence

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

<400>  48

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


<210>  49
<211>  19
<212>  PRT
<213>  Artificial Sequence

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

<400>  49

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


Pro Gly Pro 
            


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

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

<400>  50

Thr 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>  14
<212>  PRT
<213>  Artificial Sequence

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

<400>  51

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


<210>  52
<211>  17
<212>  PRT
<213>  Artificial Sequence

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

<400>  52

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


Pro 
    


<210>  53
<211>  20
<212>  PRT
<213>  Artificial Sequence

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

<400>  53

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>  54
<211>  24
<212>  PRT
<213>  Artificial Sequence

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

<400>  54

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>  55
<211>  40
<212>  PRT
<213>  Artificial Sequence

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

<400>  55

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>  56
<211>  18
<212>  PRT
<213>  Artificial Sequence

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

<400>  56

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


Gly Pro 
        


<210>  57
<211>  40
<212>  PRT
<213>  Artificial Sequence

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

<400>  57

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>  58
<211>  33
<212>  PRT
<213>  Artificial Sequence

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

<400>  58

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 
    


<210>  59
<211>  10
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Consensus Kozak sequence

<400>  59
gccrccatgg                                                              10


<210>  60
<211>  30
<212>  DNA
<213>  Homo sapiens

<400>  60
agggcgacca gaaattccca gcttctggct                                        30


<210>  61
<211>  30
<212>  DNA
<213>  Homo sapiens

<400>  61
agccagaagc tgggaatttc tggtcgccct                                        30


<210>  62
<211>  293
<212>  PRT
<213>  Ophiostoma novo-ulmi

<400>  62

Ser Ile Asn Pro Trp Ile Leu Thr Gly Phe Ala Asp Ala Glu Gly Ser 
1               5                   10                  15      


Phe Leu Leu Arg Ile Arg Asn Asn Asn Lys Ser Ser Val Gly Tyr Ser 
            20                  25                  30          


Thr Glu Leu Gly Phe Gln Ile Thr Leu His Asn Lys Asp Lys Ser Ile 
        35                  40                  45              


Leu Glu Asn Ile Gln Ser Thr Trp Lys Val Gly Val Ile Ala Asn Ser 
    50                  55                  60                  


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


Val Ile Ile Asp His Phe Glu Lys Tyr Pro Leu Ile Thr Gln Lys Leu 
                85                  90                  95      


Gly Asp Tyr Met Leu Phe Lys Gln Ala Phe Cys Val Met Glu Asn Lys 
            100                 105                 110         


Glu His Leu Lys Ile Asn Gly Ile Lys Glu Leu Val Arg Ile Lys Ala 
        115                 120                 125             


Lys Leu Asn Trp Gly Leu Thr Asp Glu Leu Lys Lys Ala Phe Pro Glu 
    130                 135                 140                 


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


Lys Trp Leu Ala Gly Phe Thr Ser Gly Glu Gly Cys Phe Phe Val Asn 
                165                 170                 175     


Leu Ile Lys Ser Lys Ser Lys Leu Gly Val Gln Val Gln Leu Val Phe 
            180                 185                 190         


Ser Ile Thr Gln His Ile Lys Asp Lys Asn Leu Met Asn Ser Leu Ile 
        195                 200                 205             


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


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


Ile Ile Pro Val Phe Gln Glu Asn Thr Leu Ile Gly Val Lys Leu Glu 
                245                 250                 255     


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


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


Met Asn Lys Gly Arg 
    290             


<210>  63
<211>  293
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized I-OnuI variant

<400>  63

Ser Ile Asn Pro Trp Ile Leu Thr Gly Phe Ala Asp Ala Glu Gly Ser 
1               5                   10                  15      


Phe Met Leu Arg Ile Arg Asn Arg Asn Gln Arg Lys Ala Asn Tyr Gly 
            20                  25                  30          


Thr Ser Leu Val Phe Glu Ile Gly Leu His Asn Lys Asp Lys Ser Ile 
        35                  40                  45              


Leu Glu Asn Ile Gln Ser Thr Trp Lys Val Gly Lys Ile Arg Asn Ser 
    50                  55                  60                  


Gly Asp Gly Ser Val Arg Leu Ser Val Thr Arg Phe Glu Asp Leu Lys 
65                  70                  75                  80  


Val Ile Ile Asp His Phe Glu Lys Tyr Pro Leu Ile Thr Gln Lys Leu 
                85                  90                  95      


Gly Asp Tyr Lys Leu Phe Lys Gln Ala Phe Ser Leu Met Glu Asn Lys 
            100                 105                 110         


Glu His Leu Lys Glu Asn Gly Ile Lys Glu Leu Val Arg Ile Lys Ala 
        115                 120                 125             


Lys Met Asn Trp Gly Leu Asn Asp Glu Leu Lys Lys Ala Phe Pro Glu 
    130                 135                 140                 


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


Lys Trp Leu Ala Gly Phe Thr Ser Gly Asp Gly Ser Phe Gly Val Asp 
                165                 170                 175     


Leu Ile Lys Arg Lys Arg Lys Thr Thr Val Gly Val Gly Leu Arg Phe 
            180                 185                 190         


Ser Ile Ser Gln His Ile Arg Asp Lys Asn Leu Met Asn Ser Leu Ile 
        195                 200                 205             


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


Ser Trp Leu Asp Phe Val Val Arg Lys Phe Ser Asp Ile Asn Asp Lys 
225                 230                 235                 240 


Ile Ile Pro Val Phe Gln Glu Asn Thr Leu Ile Gly Val Lys Leu Glu 
                245                 250                 255     


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


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


Met Asn Lys Gly Arg 
    290             


<210>  64
<211>  293
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthesized I-OnuI variant

<400>  64

Ser Ile Asn Pro Trp Ile Leu Thr Gly Phe Ala Asp Ala Glu Gly Ser 
1               5                   10                  15      


Phe Met Leu Arg Ile Arg Asn Arg Asn Gln Arg Lys Ala Asn Tyr Gly 
            20                  25                  30          


Thr Ser Leu Val Phe Glu Ile Gly Leu His Asn Lys Asp Lys Ser Ile 
        35                  40                  45              


Leu Glu Asn Ile Gln Ser Thr Trp Lys Val Gly Lys Ile Arg Asn Ser 
    50                  55                  60                  


Gly Asp Gly Ser Val Arg Leu Ser Val Thr Arg Phe Glu Asp Leu Lys 
65                  70                  75                  80  


Val Ile Ile Asp His Phe Glu Lys Tyr Pro Leu Ile Thr Gln Lys Leu 
                85                  90                  95      


Gly Asp Tyr Lys Leu Phe Lys Gln Ala Phe Ser Leu Met Glu Asn Lys 
            100                 105                 110         


Glu His Leu Lys Glu Asn Gly Ile Lys Glu Leu Val Arg Ile Lys Ala 
        115                 120                 125             


Lys Met Asn Trp Gly Leu Asn Asp Glu Leu Lys Lys Ala Phe Pro Glu 
    130                 135                 140                 


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


Lys Trp Leu Ala Gly Phe Thr Ser Gly Asp Gly Ser Phe Gly Val Asp 
                165                 170                 175     


Leu Ile Lys Arg Lys Arg Lys Thr Thr Val Gly Val Gly Leu Arg Phe 
            180                 185                 190         


Ser Ile Ser Gln His Ile Arg Asp Lys Asn Leu Met Asn Ser Leu Ile 
        195                 200                 205             


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


Ser Trp Leu Asp Phe Val Val Arg Lys Phe Ser Asp Ile Asn Asp Lys 
225                 230                 235                 240 


Ile Ile Pro Val Phe Gln Glu Asn Thr Leu Ile Gly Val Lys Leu Lys 
                245                 250                 255     


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


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


Met Asn Lys Gly Arg 
    290             


<210>  65
<211>  47
<212>  DNA
<213>  Homo sapiens

<400>  65
aacgtgttga gagatcgagg gcgaccagaa attcccagct tctggct                     47


<210>  66
<211>  47
<212>  DNA
<213>  Homo sapiens

<400>  66
agccagaagc tgggaatttc tggtcgccct cgatctctca acacgtt                     47


