                         SEQUENCE LISTING

<110>  UCL Business PLC
       Syncona Partners LLP
 
<120>  CHIMERIC PROTEIN

<130>  P106629PCT

<150>  GB 1503133.9
<151>  2015-02-24

<160>  17    

<170>  PatentIn version 3.5

<210>  1
<211>  517
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric protein FRB-FKBP12-L3-dCasp9

<400>  1

Met Ala Ser Arg Ile Leu Trp His Glu Met Trp His Glu Gly Leu Glu 
1               5                   10                  15      


Glu Ala Ser Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys Gly Met Phe 
            20                  25                  30          


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


Leu Lys Glu Thr Ser Phe Asn Gln Ala Tyr Gly Arg Asp Leu Met Glu 
    50                  55                  60                  


Ala Gln Glu Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp 
65                  70                  75                  80  


Leu Leu Gln Ala Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser 
                85                  90                  95      


Lys Leu Glu Tyr Ser Gly Gly Gly Ser Leu Glu Gly Val Gln Val Glu 
            100                 105                 110         


Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr 
        115                 120                 125             


Cys Val Val His Tyr Thr Gly Met Leu Glu Asp Gly Lys Lys Phe Asp 
    130                 135                 140                 


Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe Met Leu Gly Lys Gln 
145                 150                 155                 160 


Glu Val Ile Arg Gly Trp Glu Glu Gly Val Ala Gln Met Ser Val Gly 
                165                 170                 175     


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


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


Glu Leu Leu Lys Leu Glu Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
    210                 215                 220                 


Ser Gly Gly Gly Gly Ser Gly Val Asp Gly Phe Gly Asp Val Gly Ala 
225                 230                 235                 240 


Leu Glu Ser Leu Arg Gly Asn Ala Asp Leu Ala Tyr Ile Leu Ser Met 
                245                 250                 255     


Glu Pro Cys Gly His Cys Leu Ile Ile Asn Asn Val Asn Phe Cys Arg 
            260                 265                 270         


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


Leu Arg Arg Arg Phe Ser Ser Leu His Phe Met Val Glu Val Lys Gly 
    290                 295                 300                 


Asp Leu Thr Ala Lys Lys Met Val Leu Ala Leu Leu Glu Leu Ala Gln 
305                 310                 315                 320 


Gln Asp His Gly Ala Leu Asp Cys Cys Val Val Val Ile Leu Ser His 
                325                 330                 335     


Gly Cys Gln Ala Ser His Leu Gln Phe Pro Gly Ala Val Tyr Gly Thr 
            340                 345                 350         


Asp Gly Cys Pro Val Ser Val Glu Lys Ile Val Asn Ile Phe Asn Gly 
        355                 360                 365             


Thr Ser Cys Pro Ser Leu Gly Gly Lys Pro Lys Leu Phe Phe Ile Gln 
    370                 375                 380                 


Ala Cys Gly Gly Glu Gln Lys Asp His Gly Phe Glu Val Ala Ser Thr 
385                 390                 395                 400 


Ser Pro Glu Asp Glu Ser Pro Gly Ser Asn Pro Glu Pro Asp Ala Thr 
                405                 410                 415     


Pro Phe Gln Glu Gly Leu Arg Thr Phe Asp Gln Leu Asp Ala Ile Ser 
            420                 425                 430         


Ser Leu Pro Thr Pro Ser Asp Ile Phe Val Ser Tyr Ser Thr Phe Pro 
        435                 440                 445             


Gly Phe Val Ser Trp Arg Asp Pro Lys Ser Gly Ser Trp Tyr Val Glu 
    450                 455                 460                 


Thr Leu Asp Asp Ile Phe Glu Gln Trp Ala His Ser Glu Asp Leu Gln 
465                 470                 475                 480 


Ser Leu Leu Leu Arg Val Ala Asn Ala Val Ser Val Lys Gly Ile Tyr 
                485                 490                 495     


Lys Gln Met Pro Gly Cys Phe Asn Phe Leu Arg Lys Lys Leu Phe Phe 
            500                 505                 510         


Lys Thr Ser Ala Ser 
        515         


<210>  2
<211>  402
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric protein FKBP12-dCasp9

<400>  2

Met Leu Glu Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg 
1               5                   10                  15      


Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met 
            20                  25                  30          


Leu Glu Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro 
        35                  40                  45              


Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu 
    50                  55                  60                  


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


Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro 
                85                  90                  95      


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


Gly Gly Ser Gly Val Asp Gly Phe Gly Asp Val Gly Ala Leu Glu Ser 
        115                 120                 125             


Leu Arg Gly Asn Ala Asp Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys 
    130                 135                 140                 


Gly His Cys Leu Ile Ile Asn Asn Val Asn Phe Cys Arg Glu Ser Gly 
145                 150                 155                 160 


Leu Arg Thr Arg Thr Gly Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg 
                165                 170                 175     


Arg Phe Ser Ser Leu His Phe Met Val Glu Val Lys Gly Asp Leu Thr 
            180                 185                 190         


Ala Lys Lys Met Val Leu Ala Leu Leu Glu Leu Ala Gln Gln Asp His 
        195                 200                 205             


Gly Ala Leu Asp Cys Cys Val Val Val Ile Leu Ser His Gly Cys Gln 
    210                 215                 220                 


Ala Ser His Leu Gln Phe Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys 
225                 230                 235                 240 


Pro Val Ser Val Glu Lys Ile Val Asn Ile Phe Asn Gly Thr Ser Cys 
                245                 250                 255     


Pro Ser Leu Gly Gly Lys Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly 
            260                 265                 270         


Gly Glu Gln Lys Asp His Gly Phe Glu Val Ala Ser Thr Ser Pro Glu 
        275                 280                 285             


Asp Glu Ser Pro Gly Ser Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln 
    290                 295                 300                 


Glu Gly Leu Arg Thr Phe Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro 
305                 310                 315                 320 


Thr Pro Ser Asp Ile Phe Val Ser Tyr Ser Thr Phe Pro Gly Phe Val 
                325                 330                 335     


Ser Trp Arg Asp Pro Lys Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp 
            340                 345                 350         


Asp Ile Phe Glu Gln Trp Ala His Ser Glu Asp Leu Gln Ser Leu Leu 
        355                 360                 365             


Leu Arg Val Ala Asn Ala Val Ser Val Lys Gly Ile Tyr Lys Gln Met 
    370                 375                 380                 


Pro Gly Cys Phe Asn Phe Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser 
385                 390                 395                 400 


Ala Ser 
        


<210>  3
<211>  392
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric protein FRB-dCasp9

<400>  3

Met Ala Ser Arg Ile Leu Trp His Glu Met Trp His Glu Gly Leu Glu 
1               5                   10                  15      


Glu Ala Ser Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys Gly Met Phe 
            20                  25                  30          


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


Leu Lys Glu Thr Ser Phe Asn Gln Ala Tyr Gly Arg Asp Leu Met Glu 
    50                  55                  60                  


Ala Gln Glu Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp 
65                  70                  75                  80  


Leu Leu Gln Ala Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser 
                85                  90                  95      


Lys Leu Glu Tyr Ser Gly Gly Gly Ser Gly Val Asp Gly Phe Gly Asp 
            100                 105                 110         


Val Gly Ala Leu Glu Ser Leu Arg Gly Asn Ala Asp Leu Ala Tyr Ile 
        115                 120                 125             


Leu Ser Met Glu Pro Cys Gly His Cys Leu Ile Ile Asn Asn Val Asn 
    130                 135                 140                 


Phe Cys Arg Glu Ser Gly Leu Arg Thr Arg Thr Gly Ser Asn Ile Asp 
145                 150                 155                 160 


Cys Glu Lys Leu Arg Arg Arg Phe Ser Ser Leu His Phe Met Val Glu 
                165                 170                 175     


Val Lys Gly Asp Leu Thr Ala Lys Lys Met Val Leu Ala Leu Leu Glu 
            180                 185                 190         


Leu Ala Gln Gln Asp His Gly Ala Leu Asp Cys Cys Val Val Val Ile 
        195                 200                 205             


Leu Ser His Gly Cys Gln Ala Ser His Leu Gln Phe Pro Gly Ala Val 
    210                 215                 220                 


Tyr Gly Thr Asp Gly Cys Pro Val Ser Val Glu Lys Ile Val Asn Ile 
225                 230                 235                 240 


Phe Asn Gly Thr Ser Cys Pro Ser Leu Gly Gly Lys Pro Lys Leu Phe 
                245                 250                 255     


Phe Ile Gln Ala Cys Gly Gly Glu Gln Lys Asp His Gly Phe Glu Val 
            260                 265                 270         


Ala Ser Thr Ser Pro Glu Asp Glu Ser Pro Gly Ser Asn Pro Glu Pro 
        275                 280                 285             


Asp Ala Thr Pro Phe Gln Glu Gly Leu Arg Thr Phe Asp Gln Leu Asp 
    290                 295                 300                 


Ala Ile Ser Ser Leu Pro Thr Pro Ser Asp Ile Phe Val Ser Tyr Ser 
305                 310                 315                 320 


Thr Phe Pro Gly Phe Val Ser Trp Arg Asp Pro Lys Ser Gly Ser Trp 
                325                 330                 335     


Tyr Val Glu Thr Leu Asp Asp Ile Phe Glu Gln Trp Ala His Ser Glu 
            340                 345                 350         


Asp Leu Gln Ser Leu Leu Leu Arg Val Ala Asn Ala Val Ser Val Lys 
        355                 360                 365             


Gly Ile Tyr Lys Gln Met Pro Gly Cys Phe Asn Phe Leu Arg Lys Lys 
    370                 375                 380                 


Leu Phe Phe Lys Thr Ser Ala Ser 
385                 390         


<210>  4
<211>  651
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric protein FKBP12-dCasp9-2A-FRB-FRBw

<400>  4

Met Leu Glu Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg 
1               5                   10                  15      


Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met 
            20                  25                  30          


Leu Glu Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro 
        35                  40                  45              


Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu 
    50                  55                  60                  


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


Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro 
                85                  90                  95      


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


Gly Gly Ser Gly Val Asp Gly Phe Gly Asp Val Gly Ala Leu Glu Ser 
        115                 120                 125             


Leu Arg Gly Asn Ala Asp Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys 
    130                 135                 140                 


Gly His Cys Leu Ile Ile Asn Asn Val Asn Phe Cys Arg Glu Ser Gly 
145                 150                 155                 160 


Leu Arg Thr Arg Thr Gly Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg 
                165                 170                 175     


Arg Phe Ser Ser Leu His Phe Met Val Glu Val Lys Gly Asp Leu Thr 
            180                 185                 190         


Ala Lys Lys Met Val Leu Ala Leu Leu Glu Leu Ala Gln Gln Asp His 
        195                 200                 205             


Gly Ala Leu Asp Cys Cys Val Val Val Ile Leu Ser His Gly Cys Gln 
    210                 215                 220                 


Ala Ser His Leu Gln Phe Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys 
225                 230                 235                 240 


Pro Val Ser Val Glu Lys Ile Val Asn Ile Phe Asn Gly Thr Ser Cys 
                245                 250                 255     


Pro Ser Leu Gly Gly Lys Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly 
            260                 265                 270         


Gly Glu Gln Lys Asp His Gly Phe Glu Val Ala Ser Thr Ser Pro Glu 
        275                 280                 285             


Asp Glu Ser Pro Gly Ser Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln 
    290                 295                 300                 


Glu Gly Leu Arg Thr Phe Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro 
305                 310                 315                 320 


Thr Pro Ser Asp Ile Phe Val Ser Tyr Ser Thr Phe Pro Gly Phe Val 
                325                 330                 335     


Ser Trp Arg Asp Pro Lys Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp 
            340                 345                 350         


Asp Ile Phe Glu Gln Trp Ala His Ser Glu Asp Leu Gln Ser Leu Leu 
        355                 360                 365             


Leu Arg Val Ala Asn Ala Val Ser Val Lys Gly Ile Tyr Lys Gln Met 
    370                 375                 380                 


Pro Gly Cys Phe Asn Phe Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser 
385                 390                 395                 400 


Ala Ser Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp Val 
                405                 410                 415     


Glu Ser Asn Pro Gly Pro Gly Val Gln Val Glu Thr Ile Ser Pro Gly 
            420                 425                 430         


Asp Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr 
        435                 440                 445             


Thr Gly Met Leu Glu Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg 
    450                 455                 460                 


Asn Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly 
465                 470                 475                 480 


Trp Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu 
                485                 490                 495     


Thr Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile 
            500                 505                 510         


Ile Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu 
        515                 520                 525             


Glu Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Met Leu Glu Gly 
    530                 535                 540                 


Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro Lys 
545                 550                 555                 560 


Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp Gly 
                565                 570                 575     


Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe Met 
            580                 585                 590         


Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val Ala Gln 
        595                 600                 605             


Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr Ala 
    610                 615                 620                 


Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr Leu 
625                 630                 635                 640 


Val Phe Asp Val Glu Leu Leu Lys Leu Glu Ser 
                645                 650     


<210>  5
<211>  416
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Asp Glu Ala Asp Arg Arg Leu Leu Arg Arg Cys Arg Leu Arg Leu 
1               5                   10                  15      


Val Glu Glu Leu Gln Val Asp Gln Leu Trp Asp Ala Leu Leu Ser Ser 
            20                  25                  30          


Glu Leu Phe Arg Pro His Met Ile Glu Asp Ile Gln Arg Ala Gly Ser 
        35                  40                  45              


Gly Ser Arg Arg Asp Gln Ala Arg Gln Leu Ile Ile Asp Leu Glu Thr 
    50                  55                  60                  


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


Gly Gln Asp Met Leu Ala Ser Phe Leu Arg Thr Asn Arg Gln Ala Ala 
                85                  90                  95      


Lys Leu Ser Lys Pro Thr Leu Glu Asn Leu Thr Pro Val Val Leu Arg 
            100                 105                 110         


Pro Glu Ile Arg Lys Pro Glu Val Leu Arg Pro Glu Thr Pro Arg Pro 
        115                 120                 125             


Val Asp Ile Gly Ser Gly Gly Phe Gly Asp Val Gly Ala Leu Glu Ser 
    130                 135                 140                 


Leu Arg Gly Asn Ala Asp Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys 
145                 150                 155                 160 


Gly His Cys Leu Ile Ile Asn Asn Val Asn Phe Cys Arg Glu Ser Gly 
                165                 170                 175     


Leu Arg Thr Arg Thr Gly Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg 
            180                 185                 190         


Arg Phe Ser Ser Pro His Phe Met Val Glu Val Lys Gly Asp Leu Thr 
        195                 200                 205             


Ala Lys Lys Met Val Leu Ala Leu Leu Glu Leu Ala Gln Gln Asp His 
    210                 215                 220                 


Gly Ala Leu Asp Cys Cys Val Val Val Ile Leu Ser His Gly Cys Gln 
225                 230                 235                 240 


Ala Ser His Leu Gln Phe Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys 
                245                 250                 255     


Pro Val Ser Val Glu Lys Ile Val Asn Ile Phe Asn Gly Thr Ser Cys 
            260                 265                 270         


Pro Ser Leu Gly Gly Lys Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly 
        275                 280                 285             


Gly Glu Gln Lys Asp His Gly Phe Glu Val Ala Ser Thr Ser Pro Glu 
    290                 295                 300                 


Asp Glu Ser Pro Gly Ser Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln 
305                 310                 315                 320 


Glu Gly Leu Arg Thr Phe Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro 
                325                 330                 335     


Thr Pro Ser Asp Ile Phe Val Ser Tyr Ser Thr Phe Pro Gly Phe Val 
            340                 345                 350         


Ser Trp Arg Asp Pro Lys Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp 
        355                 360                 365             


Asp Ile Phe Glu Gln Trp Ala His Ser Glu Asp Leu Gln Ser Leu Leu 
    370                 375                 380                 


Leu Arg Val Ala Asn Ala Val Ser Val Lys Gly Ile Tyr Lys Gln Met 
385                 390                 395                 400 


Pro Gly Cys Phe Asn Phe Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser 
                405                 410                 415     


<210>  6
<211>  282
<212>  PRT
<213>  Homo sapiens

<400>  6

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


Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys Gly His Cys Leu Ile Ile 
            20                  25                  30          


Asn Asn Val Asn Phe Cys Arg Glu Ser Gly Leu Arg Thr Arg Thr Gly 
        35                  40                  45              


Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg Arg Phe Ser Ser Leu His 
    50                  55                  60                  


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


Ala Leu Leu Glu Leu Ala Gln Gln Asp His Gly Ala Leu Asp Cys Cys 
                85                  90                  95      


Val Val Val Ile Leu Ser His Gly Cys Gln Ala Ser His Leu Gln Phe 
            100                 105                 110         


Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys Pro Val Ser Val Glu Lys 
        115                 120                 125             


Ile Val Asn Ile Phe Asn Gly Thr Ser Cys Pro Ser Leu Gly Gly Lys 
    130                 135                 140                 


Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly Gly Glu Gln Lys Asp His 
145                 150                 155                 160 


Gly Phe Glu Val Ala Ser Thr Ser Pro Glu Asp Glu Ser Pro Gly Ser 
                165                 170                 175     


Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln Glu Gly Leu Arg Thr Phe 
            180                 185                 190         


Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro Thr Pro Ser Asp Ile Phe 
        195                 200                 205             


Val Ser Tyr Ser Thr Phe Pro Gly Phe Val Ser Trp Arg Asp Pro Lys 
    210                 215                 220                 


Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp Asp Ile Phe Glu Gln Trp 
225                 230                 235                 240 


Ala His Ser Glu Asp Leu Gln Ser Leu Leu Leu Arg Val Ala Asn Ala 
                245                 250                 255     


Val Ser Val Lys Gly Ile Tyr Lys Gln Met Pro Gly Cys Phe Asn Phe 
            260                 265                 270         


Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser 
        275                 280         


<210>  7
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FKBP12 domain

<400>  7

Met Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe 
1               5                   10                  15      


Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu 
            20                  25                  30          


Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys 
        35                  40                  45              


Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val 
    50                  55                  60                  


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


Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala 
                85                  90                  95      


Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu 
            100                 105             


<210>  8
<211>  100
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  wild-type FRB segment of mTOR

<400>  8

Met Ala Ser Arg Ile Leu Trp His Glu Met Trp His Glu Gly Leu Glu 
1               5                   10                  15      


Glu Ala Ser Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys Gly Met Phe 
            20                  25                  30          


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


Leu Lys Glu Thr Ser Phe Asn Gln Ala Tyr Gly Arg Asp Leu Met Glu 
    50                  55                  60                  


Ala Gln Glu Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp 
65                  70                  75                  80  


Leu Thr Gln Ala Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser 
                85                  90                  95      


Lys Leu Glu Ser 
            100 


<210>  9
<211>  100
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FRB with T to L substitution at 2098 which allows binding to 
       AP21967

<400>  9

Met Ala Ser Arg Ile Leu Trp His Glu Met Trp His Glu Gly Leu Glu 
1               5                   10                  15      


Glu Ala Ser Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys Gly Met Phe 
            20                  25                  30          


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


Leu Lys Glu Thr Ser Phe Asn Gln Ala Tyr Gly Arg Asp Leu Met Glu 
    50                  55                  60                  


Ala Gln Glu Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp 
65                  70                  75                  80  


Leu Leu Gln Ala Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser 
                85                  90                  95      


Lys Leu Glu Ser 
            100 


<210>  10
<211>  100
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FRB segment of mTOR with T to H substitution at 2098 and to W at 
       F at residue 2101 of the full mTOR

<400>  10

Met Ala Ser Arg Ile Leu Trp His Glu Met Trp His Glu Gly Leu Glu 
1               5                   10                  15      


Glu Ala Ser Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys Gly Met Phe 
            20                  25                  30          


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


Leu Lys Glu Thr Ser Phe Asn Gln Ala Tyr Gly Arg Asp Leu Met Glu 
    50                  55                  60                  


Ala Gln Glu Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp 
65                  70                  75                  80  


Leu His Gln Ala Phe Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser 
                85                  90                  95      


Lys Leu Glu Ser 
            100 


<210>  11
<211>  100
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FRB segment of mTOR with K to P substitution at residue 2095 of 
       the full mTOR

<400>  11

Met Ala Ser Arg Ile Leu Trp His Glu Met Trp His Glu Gly Leu Glu 
1               5                   10                  15      


Glu Ala Ser Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys Gly Met Phe 
            20                  25                  30          


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


Leu Lys Glu Thr Ser Phe Asn Gln Ala Tyr Gly Arg Asp Leu Met Glu 
    50                  55                  60                  


Ala Gln Glu Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Pro Asp 
65                  70                  75                  80  


Leu Thr Gln Ala Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser 
                85                  90                  95      


Lys Leu Glu Ser 
            100 


<210>  12
<211>  1554
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FRB-FKBP12-L3-Casp9 nucleotide sequence

<400>  12
atggcttcta gaatcctctg gcatgagatg tggcatgaag gcctggaaga ggcatctcgt       60

ttgtactttg gggaaaggaa cgtgaaaggc atgtttgagg tgctggagcc cttgcatgct      120

atgatggaac ggggccccca gactctgaag gaaacatcct ttaatcaggc ctatggtcga      180

gatttaatgg aggcccaaga gtggtgcagg aagtacatga aatcagggaa tgtcaaggac      240

ctcctccaag cctgggacct ctattatcat gtgttccgac gaatctcaaa gctcgagtat      300

agcggcggcg gcagcctgga gggcgtgcag gtggagacca tcagcccagg cgacggcaga      360

accttcccca agagaggcca gacctgcgtg gtgcactata ccggcatgct ggaggacggc      420

aagaagttcg acagcagccg cgaccgcaat aagcccttca agttcatgct gggcaagcag      480

gaggtgatca gaggctggga ggagggcgtg gcccagatga gcgtgggcca gagagccaag      540

ctgaccatca gccccgacta cgcctatggc gccaccggcc accccggcat catcccaccc      600

cacgccaccc tggtgtttga tgtggagctg ctgaagctgg agtccggcgg aggcgggtct      660

ggaggaggcg gcagcggcgg cggcgggtca ggcgtggatg gcttcggcga cgtgggagcc      720

ctggagagcc tgagaggcaa cgccgatctg gcctacatcc tgagcatgga gccctgtggc      780

cactgcctga tcatcaacaa cgtgaacttc tgccgggaga gcggcctgcg gacccggacc      840

ggcagcaaca tcgactgcga gaagctgagg aggcgcttct cctccctgca ctttatggtg      900

gaggtgaaag gcgatctgac tgccaagaaa atggtgctgg ccctgctgga gctggcccag      960

caggaccacg gagccctgga ttgctgtgtg gtggtgatcc tgtcccacgg ctgccaggcc     1020

agccacctgc agttccccgg agccgtgtac ggcaccgacg gctgtcccgt gtccgtggag     1080

aagatcgtga acatcttcaa cggcacctcc tgcccctccc tgggcggcaa gcccaagctg     1140

ttctttatcc aggcctgtgg cggcgagcag aaggaccacg gctttgaggt ggccagcacc     1200

tcccccgagg acgagagccc aggcagcaac cccgagcccg acgccacccc cttccaggag     1260

ggcctgcgca ccttcgacca gctggacgcc atcagcagcc tgcccacccc cagcgacatc     1320

ttcgtgagct acagcacctt tcccggcttc gtgagctggc gcgatcccaa gtccggctct     1380

tggtatgtgg agaccctgga cgacatcttt gagcagtggg ctcatagcga ggacctgcag     1440

agcctgctgc tgcgcgtggc caatgccgtg agcgtgaagg gcatctacaa gcagatgcca     1500

ggctgcttca acttcctgcg gaagaagctg ttcttcaaga ccagcgcctc ctga           1554


<210>  13
<211>  1209
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FKBP12-dCasp9 nucleotide sequence

<400>  13
atgctggagg gcgtgcaggt ggagaccatc agcccaggcg acggcagaac cttccccaag       60

agaggccaga cctgcgtggt gcactatacc ggcatgctgg aggacggcaa gaagttcgac      120

agcagccgcg accgcaataa gcccttcaag ttcatgctgg gcaagcagga ggtgatcaga      180

ggctgggagg agggcgtggc ccagatgagc gtgggccaga gagccaagct gaccatcagc      240

cccgactacg cctatggcgc caccggccac cccggcatca tcccacccca cgccaccctg      300

gtgtttgatg tggagctgct gaagctggag tccggaggcg gctccggcgt ggatggcttc      360

ggcgacgtgg gagccctgga gagcctgaga ggcaacgccg atctggccta catcctgagc      420

atggagccct gtggccactg cctgatcatc aacaacgtga acttctgccg ggagagcggc      480

ctgcggaccc ggaccggcag caacatcgac tgcgagaagc tgaggaggcg cttctcctcc      540

ctgcacttta tggtggaggt gaaaggcgat ctgactgcca agaaaatggt gctggccctg      600

ctggagctgg cccagcagga ccacggagcc ctggattgct gtgtggtggt gatcctgtcc      660

cacggctgcc aggccagcca cctgcagttc cccggagccg tgtacggcac cgacggctgt      720

cccgtgtccg tggagaagat cgtgaacatc ttcaacggca cctcctgccc ctccctgggc      780

ggcaagccca agctgttctt tatccaggcc tgtggcggcg agcagaagga ccacggcttt      840

gaggtggcca gcacctcccc cgaggacgag agcccaggca gcaaccccga gcccgacgcc      900

acccccttcc aggagggcct gcgcaccttc gaccagctgg acgccatcag cagcctgccc      960

acccccagcg acatcttcgt gagctacagc acctttcccg gcttcgtgag ctggcgcgat     1020

cccaagtccg gctcttggta tgtggagacc ctggacgaca tctttgagca gtgggctcat     1080

agcgaggacc tgcagagcct gctgctgcgc gtggccaatg ccgtgagcgt gaagggcatc     1140

tacaagcaga tgccaggctg cttcaacttc ctgcggaaga agctgttctt caagaccagc     1200

gcctcctga                                                             1209


<210>  14
<211>  1179
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FRB-dCasp9 nucleotide sequence

<400>  14
atggcttcta gaatcctctg gcatgagatg tggcatgaag gcctggaaga ggcatctcgt       60

ttgtactttg gggaaaggaa cgtgaaaggc atgtttgagg tgctggagcc cttgcatgct      120

atgatggaac ggggccccca gactctgaag gaaacatcct ttaatcaggc ctatggtcga      180

gatttaatgg aggcccaaga gtggtgcagg aagtacatga aatcagggaa tgtcaaggac      240

ctcctccaag cctgggacct ctattatcat gtgttccgac gaatctcaaa gctcgagtat      300

agcggcggcg gcagcggcgt ggatggcttc ggcgacgtgg gagccctgga gagcctgaga      360

ggcaacgccg atctggccta catcctgagc atggagccct gtggccactg cctgatcatc      420

aacaacgtga acttctgccg ggagagcggc ctgcggaccc ggaccggcag caacatcgac      480

tgcgagaagc tgaggaggcg cttctcctcc ctgcacttta tggtggaggt gaaaggcgat      540

ctgactgcca agaaaatggt gctggccctg ctggagctgg cccagcagga ccacggagcc      600

ctggattgct gtgtggtggt gatcctgtcc cacggctgcc aggccagcca cctgcagttc      660

cccggagccg tgtacggcac cgacggctgt cccgtgtccg tggagaagat cgtgaacatc      720

ttcaacggca cctcctgccc ctccctgggc ggcaagccca agctgttctt tatccaggcc      780

tgtggcggcg agcagaagga ccacggcttt gaggtggcca gcacctcccc cgaggacgag      840

agcccaggca gcaaccccga gcccgacgcc acccccttcc aggagggcct gcgcaccttc      900

gaccagctgg acgccatcag cagcctgccc acccccagcg acatcttcgt gagctacagc      960

acctttcccg gcttcgtgag ctggcgcgat cccaagtccg gctcttggta tgtggagacc     1020

ctggacgaca tctttgagca gtgggctcat agcgaggacc tgcagagcct gctgctgcgc     1080

gtggccaatg ccgtgagcgt gaagggcatc tacaagcaga tgccaggctg cttcaacttc     1140

ctgcggaaga agctgttctt caagaccagc gcctcctga                            1179


<210>  15
<211>  1956
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FKBP12-Casp9-2A-FRB-FRBw nucleotide sequence

<400>  15
atgctggagg gcgtgcaggt ggagaccatc agcccaggcg acggcagaac cttccccaag       60

agaggccaga cctgcgtggt gcactatacc ggcatgctgg aggacggcaa gaagttcgac      120

agcagccgcg accgcaataa gcccttcaag ttcatgctgg gcaagcagga ggtgatcaga      180

ggctgggagg agggcgtggc ccagatgagc gtgggccaga gagccaagct gaccatcagc      240

cccgactacg cctatggcgc caccggccac cccggcatca tcccacccca cgccaccctg      300

gtgtttgatg tggagctgct gaagctggag tccggaggcg gctccggcgt ggatggcttc      360

ggcgacgtgg gagccctgga gagcctgaga ggcaacgccg atctggccta catcctgagc      420

atggagccct gtggccactg cctgatcatc aacaacgtga acttctgccg ggagagcggc      480

ctgcggaccc ggaccggcag caacatcgac tgcgagaagc tgaggaggcg cttctcctcc      540

ctgcacttta tggtggaggt gaaaggcgat ctgactgcca agaaaatggt gctggccctg      600

ctggagctgg cccagcagga ccacggagcc ctggattgct gtgtggtggt gatcctgtcc      660

cacggctgcc aggccagcca cctgcagttc cccggagccg tgtacggcac cgacggctgt      720

cccgtgtccg tggagaagat cgtgaacatc ttcaacggca cctcctgccc ctccctgggc      780

ggcaagccca agctgttctt tatccaggcc tgtggcggcg agcagaagga ccacggcttt      840

gaggtggcca gcacctcccc cgaggacgag agcccaggca gcaaccccga gcccgacgcc      900

acccccttcc aggagggcct gcgcaccttc gaccagctgg acgccatcag cagcctgccc      960

acccccagcg acatcttcgt gagctacagc acctttcccg gcttcgtgag ctggcgcgat     1020

cccaagtccg gctcttggta tgtggagacc ctggacgaca tctttgagca gtgggctcat     1080

agcgaggacc tgcagagcct gctgctgcgc gtggccaatg ccgtgagcgt gaagggcatc     1140

tacaagcaga tgccaggctg cttcaacttc ctgcggaaga agctgttctt caagaccagc     1200

gcctcccagt gcaccaatta tgctttgctt aagctggcag gcgatgtgga atcaaacccg     1260

ggtcctgggg tacaggtgga gaccatctct cctggcgacg ggagaacatt tcctaaaagg     1320

ggccaaacat gcgtggttca ctataccggt atgctggagg atggcaaaaa agtagactcc     1380

agccgggata gaaacaaacc ctttaagttc atgctgggta agcaggaagt tatacggggc     1440

tgggaagagg gagtagctca gatgtctgtg ggccagaggg ccaagctgac catctcaccg     1500

gactacgcct acggcgctac cggccaccct ggcattatac caccccatgc aactctcgtc     1560

ttcgatgttg agttgctcaa actggaatca ggcggaggcg ggtctggagg aggcggcagc     1620

atgctggagg gcgtgcaggt ggagaccatc agcccaggcg acggcagaac cttccccaag     1680

agaggccaga cctgcgtggt gcactatacc ggcatgctgg aggacggcaa gaagttcgac     1740

agcagccgcg accgcaataa gcccttcaag ttcatgctgg gcaagcagga ggtgatcaga     1800

ggctgggagg agggcgtggc ccagatgagc gtgggccaga gagccaagct gaccatcagc     1860

cccgactacg cctatggcgc caccggccac cccggcatca tcccacccca cgccaccctg     1920

gtgtttgatg tggagctgct gaagctggag tcctga                               1956


<210>  16
<211>  20
<212>  PRT
<213>  Foot-and-mouth disease virus

<400>  16

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


Asn Pro Gly Pro 
            20  


<210>  17
<211>  20
<212>  PRT
<213>  Foot-and-mouth disease virus

<400>  17

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  


