                         SEQUENCE LISTING

<110>  Dorian Therapeutics, Inc.
 
<120>  METHODS AND COMPOSITIONS FOR MODULATING CELLULAR AGING

<130>  DOTH-001/01WO 335444-2003

<150>  US 62/893,618
<151>  2019-08-29

<160>  13    

<170>  PatentIn version 3.5

<210>  1
<211>  823
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Gly Lys Lys Arg Thr Lys Gly Lys Thr Val Pro Ile Asp Asp Ser 
1               5                   10                  15      


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


Gln Gly Asn Leu Lys Lys Ala Leu Val Asn Val Glu Trp Asn Ile Cys 
        35                  40                  45              


Gln Asp Cys Lys Thr Asp Asn Lys Val Lys Asp Lys Ala Glu Glu Glu 
    50                  55                  60                  


Thr Glu Glu Lys Pro Ser Val Trp Leu Cys Leu Lys Cys Gly His Gln 
65                  70                  75                  80  


Gly Cys Gly Arg Asn Ser Gln Glu Gln His Ala Leu Lys His Tyr Leu 
                85                  90                  95      


Thr Pro Arg Ser Glu Pro His Cys Leu Val Leu Ser Leu Asp Asn Trp 
            100                 105                 110         


Ser Val Trp Cys Tyr Val Cys Asp Asn Glu Val Gln Tyr Cys Ser Ser 
        115                 120                 125             


Asn Gln Leu Gly Gln Val Val Asp Tyr Val Arg Lys Gln Ala Ser Ile 
    130                 135                 140                 


Thr Thr Pro Lys Pro Ala Glu Lys Asp Asn Gly Asn Ile Glu Leu Glu 
145                 150                 155                 160 


Asn Lys Lys Leu Glu Lys Glu Ser Lys Asn Glu Gln Glu Arg Glu Lys 
                165                 170                 175     


Lys Glu Asn Met Ala Lys Glu Asn Pro Pro Met Asn Ser Pro Cys Gln 
            180                 185                 190         


Ile Thr Val Lys Gly Leu Ser Asn Leu Gly Asn Thr Cys Phe Phe Asn 
        195                 200                 205             


Ala Val Met Gln Asn Leu Ser Gln Thr Pro Val Leu Arg Glu Leu Leu 
    210                 215                 220                 


Lys Glu Val Lys Met Ser Gly Thr Ile Val Lys Ile Glu Pro Pro Asp 
225                 230                 235                 240 


Leu Ala Leu Thr Glu Pro Leu Glu Ile Asn Leu Glu Pro Pro Gly Pro 
                245                 250                 255     


Leu Thr Leu Ala Met Ser Gln Phe Leu Asn Glu Met Gln Glu Thr Lys 
            260                 265                 270         


Lys Gly Val Val Thr Pro Lys Glu Leu Phe Ser Gln Val Cys Lys Lys 
        275                 280                 285             


Ala Val Arg Phe Lys Gly Tyr Gln Gln Gln Asp Ser Gln Glu Leu Leu 
    290                 295                 300                 


Arg Tyr Leu Leu Asp Gly Met Arg Ala Glu Glu His Gln Arg Val Ser 
305                 310                 315                 320 


Lys Gly Ile Leu Lys Ala Phe Gly Asn Ser Thr Glu Lys Leu Asp Glu 
                325                 330                 335     


Glu Leu Lys Asn Lys Val Lys Asp Tyr Glu Lys Lys Lys Ser Met Pro 
            340                 345                 350         


Ser Phe Val Asp Arg Ile Phe Gly Gly Glu Leu Thr Ser Met Ile Met 
        355                 360                 365             


Cys Asp Gln Cys Arg Thr Val Ser Leu Val His Glu Ser Phe Leu Asp 
    370                 375                 380                 


Leu Ser Leu Pro Val Leu Asp Asp Gln Ser Gly Lys Lys Ser Val Asn 
385                 390                 395                 400 


Asp Lys Asn Leu Lys Lys Thr Val Glu Asp Glu Asp Gln Asp Ser Glu 
                405                 410                 415     


Glu Glu Lys Asp Asn Asp Ser Tyr Ile Lys Glu Arg Ser Asp Ile Pro 
            420                 425                 430         


Ser Gly Thr Ser Lys His Leu Gln Lys Lys Ala Lys Lys Gln Ala Lys 
        435                 440                 445             


Lys Gln Ala Lys Asn Gln Arg Arg Gln Gln Lys Ile Gln Gly Lys Val 
    450                 455                 460                 


Leu His Leu Asn Asp Ile Cys Thr Ile Asp His Pro Glu Asp Ser Glu 
465                 470                 475                 480 


Tyr Glu Ala Glu Met Ser Leu Gln Gly Glu Val Asn Ile Lys Ser Asn 
                485                 490                 495     


His Ile Ser Gln Glu Gly Val Met His Lys Glu Tyr Cys Val Asn Gln 
            500                 505                 510         


Lys Asp Leu Asn Gly Gln Ala Lys Met Ile Glu Ser Val Thr Asp Asn 
        515                 520                 525             


Gln Lys Ser Thr Glu Glu Val Asp Met Lys Asn Ile Asn Met Asp Asn 
    530                 535                 540                 


Asp Leu Glu Val Leu Thr Ser Ser Pro Thr Arg Asn Leu Asn Gly Ala 
545                 550                 555                 560 


Tyr Leu Thr Glu Gly Ser Asn Gly Glu Val Asp Ile Ser Asn Gly Phe 
                565                 570                 575     


Lys Asn Leu Asn Leu Asn Ala Ala Leu His Pro Asp Glu Ile Asn Ile 
            580                 585                 590         


Glu Ile Leu Asn Asp Ser His Thr Pro Gly Thr Lys Val Tyr Glu Val 
        595                 600                 605             


Val Asn Glu Asp Pro Glu Thr Ala Phe Cys Thr Leu Ala Asn Arg Glu 
    610                 615                 620                 


Val Phe Asn Thr Asp Glu Cys Ser Ile Gln His Cys Leu Tyr Gln Phe 
625                 630                 635                 640 


Thr Arg Asn Glu Lys Leu Arg Asp Ala Asn Lys Leu Leu Cys Glu Val 
                645                 650                 655     


Cys Thr Arg Arg Gln Cys Asn Gly Pro Lys Ala Asn Ile Lys Gly Glu 
            660                 665                 670         


Arg Lys His Val Tyr Thr Asn Ala Lys Lys Gln Met Leu Ile Ser Leu 
        675                 680                 685             


Ala Pro Pro Val Leu Thr Leu His Leu Lys Arg Phe Gln Gln Ala Gly 
    690                 695                 700                 


Phe Asn Leu Arg Lys Val Asn Lys His Ile Lys Phe Pro Glu Ile Leu 
705                 710                 715                 720 


Asp Leu Ala Pro Phe Cys Thr Leu Lys Cys Lys Asn Val Ala Glu Glu 
                725                 730                 735     


Asn Thr Arg Val Leu Tyr Ser Leu Tyr Gly Val Val Glu His Ser Gly 
            740                 745                 750         


Thr Met Arg Ser Gly His Tyr Thr Ala Tyr Ala Lys Ala Arg Thr Ala 
        755                 760                 765             


Asn Ser His Leu Ser Asn Leu Val Leu His Gly Asp Ile Pro Gln Asp 
    770                 775                 780                 


Phe Glu Met Glu Ser Lys Gly Gln Trp Phe His Ile Ser Asp Thr His 
785                 790                 795                 800 


Val Gln Ala Val Pro Thr Thr Lys Val Leu Asn Ser Gln Ala Tyr Leu 
                805                 810                 815     


Leu Phe Tyr Glu Arg Ile Leu 
            820             


<210>  2
<211>  19
<212>  DNA
<213>  Unknown

<220>
<223>  USP16 shRNA target sequence

<400>  2
tccagaagga atatcactt                                                    19


<210>  3
<211>  823
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  USP16 protein variant

<400>  3

Met Gly Lys Lys Arg Thr Lys Gly Lys Thr Val Pro Ile Asp Asp Ser 
1               5                   10                  15      


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


Gln Gly Asn Leu Lys Lys Ala Leu Val Asn Val Glu Trp Asn Ile Cys 
        35                  40                  45              


Gln Asp Cys Lys Thr Asp Asn Lys Val Lys Asp Lys Ala Glu Glu Glu 
    50                  55                  60                  


Thr Glu Glu Lys Pro Ser Val Trp Leu Cys Leu Lys Cys Gly His Gln 
65                  70                  75                  80  


Gly Cys Gly Arg Asn Ser Gln Glu Gln His Ala Leu Lys His Tyr Leu 
                85                  90                  95      


Thr Pro Arg Ser Glu Pro His Cys Leu Val Leu Ser Leu Asp Asn Trp 
            100                 105                 110         


Ser Val Trp Cys Tyr Val Cys Asp Asn Glu Val Gln Tyr Cys Ser Ser 
        115                 120                 125             


Asn Gln Leu Gly Gln Val Val Asp Tyr Val Arg Lys Gln Ala Ser Ile 
    130                 135                 140                 


Thr Thr Pro Lys Pro Ala Glu Lys Asp Asn Gly Asn Ile Glu Leu Glu 
145                 150                 155                 160 


Asn Lys Lys Leu Glu Lys Glu Ser Lys Asn Glu Gln Glu Arg Glu Lys 
                165                 170                 175     


Lys Glu Asn Met Ala Lys Glu Asn Pro Pro Met Asn Ser Pro Cys Gln 
            180                 185                 190         


Ile Thr Val Lys Gly Leu Ser Asn Leu Gly Asn Thr Cys Phe Phe Asn 
        195                 200                 205             


Ala Val Met Gln Asn Leu Ser Gln Thr Pro Val Leu Arg Glu Leu Leu 
    210                 215                 220                 


Lys Glu Val Lys Met Ser Gly Thr Ile Val Lys Ile Glu Pro Pro Asp 
225                 230                 235                 240 


Leu Ala Leu Thr Glu Pro Leu Glu Ile Asn Leu Glu Pro Pro Gly Pro 
                245                 250                 255     


Leu Thr Leu Ala Met Ser Gln Phe Leu Asn Glu Met Gln Glu Thr Lys 
            260                 265                 270         


Lys Gly Val Val Thr Pro Lys Glu Leu Phe Ser Gln Val Cys Lys Lys 
        275                 280                 285             


Ala Val Arg Phe Lys Gly Tyr Gln Gln Gln Asp Ser Gln Glu Leu Leu 
    290                 295                 300                 


Arg Tyr Leu Leu Asp Gly Met Arg Ala Glu Glu His Gln Arg Val Ser 
305                 310                 315                 320 


Lys Gly Ile Leu Lys Ala Phe Gly Asn Ser Thr Glu Lys Leu Asp Glu 
                325                 330                 335     


Glu Leu Lys Asn Lys Val Lys Asp Tyr Glu Lys Lys Lys Ser Met Pro 
            340                 345                 350         


Ser Phe Val Asp Arg Ile Phe Gly Gly Glu Leu Thr Ser Met Ile Met 
        355                 360                 365             


Cys Asp Gln Cys Arg Thr Val Ser Leu Val His Glu Ser Phe Leu Asp 
    370                 375                 380                 


Leu Ser Leu Pro Val Leu Asp Asp Gln Ser Gly Lys Lys Ser Val Asn 
385                 390                 395                 400 


Asp Lys Asn Leu Lys Lys Thr Val Glu Asp Glu Asp Gln Asp Ser Glu 
                405                 410                 415     


Glu Glu Lys Asp Asn Asp Ser Tyr Ile Lys Glu Arg Ser Asp Ile Pro 
            420                 425                 430         


Ser Gly Thr Ser Lys His Leu Gln Lys Lys Ala Lys Lys Gln Ala Lys 
        435                 440                 445             


Lys Gln Ala Lys Asn Gln Arg Arg Gln Gln Lys Ile Gln Gly Lys Val 
    450                 455                 460                 


Leu His Leu Asn Asp Ile Cys Thr Ile Asp His Pro Glu Asp Ser Glu 
465                 470                 475                 480 


Tyr Glu Ala Glu Met Ser Leu Gln Gly Glu Val Asn Ile Lys Ser Asn 
                485                 490                 495     


His Ile Ser Gln Glu Gly Val Met His Lys Glu Tyr Cys Val Asn Gln 
            500                 505                 510         


Lys Asp Leu Asn Gly Gln Ala Lys Met Ile Glu Ser Val Thr Asp Asn 
        515                 520                 525             


Gln Lys Ser Thr Glu Glu Val Asp Met Lys Asn Ile Asn Met Asp Asn 
    530                 535                 540                 


Asp Leu Glu Val Leu Thr Ser Ser Pro Thr Arg Asn Leu Asn Gly Ala 
545                 550                 555                 560 


Tyr Leu Thr Glu Gly Ser Asn Gly Glu Val Asp Ile Ser Asn Gly Phe 
                565                 570                 575     


Lys Asn Leu Asn Leu Asn Ala Ala Leu His Pro Asp Glu Ile Asn Ile 
            580                 585                 590         


Glu Ile Leu Asn Asp Ser His Thr Pro Gly Thr Lys Val Tyr Glu Val 
        595                 600                 605             


Val Asn Glu Asp Pro Glu Thr Ala Phe Cys Thr Leu Ala Asn Arg Glu 
    610                 615                 620                 


Val Phe Asn Thr Asp Glu Cys Ser Ile Gln His Cys Leu Tyr Gln Phe 
625                 630                 635                 640 


Thr Arg Asn Glu Lys Leu Arg Asp Ala Asn Lys Leu Leu Cys Glu Val 
                645                 650                 655     


Cys Thr Arg Arg Gln Cys Asn Gly Pro Lys Ala Asn Ile Lys Gly Glu 
            660                 665                 670         


Arg Lys His Val Tyr Thr Asn Ala Lys Lys Gln Met Leu Ile Ser Leu 
        675                 680                 685             


Ala Pro Pro Val Leu Thr Leu His Leu Lys Arg Phe Gln Gln Ala Gly 
    690                 695                 700                 


Phe Asn Leu Arg Lys Val Asn Lys His Ile Lys Phe Pro Glu Ile Leu 
705                 710                 715                 720 


Asp Leu Ala Pro Phe Cys Thr Leu Lys Cys Lys Asn Val Ala Glu Glu 
                725                 730                 735     


Asn Thr Arg Val Leu Tyr Ser Leu Tyr Gly Val Val Glu His Ser Gly 
            740                 745                 750         


Thr Met Arg Ser Gly His Tyr Thr Ala Tyr Ala Lys Ala Arg Thr Ala 
        755                 760                 765             


Asn Ser His Leu Ser Asn Leu Val Leu His Gly Asp Ile Pro Gln Asp 
    770                 775                 780                 


Phe Glu Met Glu Ser Lys Gly Gln Trp Phe His Ile Ser Asp Thr His 
785                 790                 795                 800 


Val Gln Ala Val Pro Thr Thr Lys Val Leu Asn Ser Gln Ala Tyr Leu 
                805                 810                 815     


Leu Phe Tyr Glu Arg Ile Leu 
            820             


<210>  4
<211>  823
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  USP16 protein variant

<400>  4

Met Gly Lys Lys Arg Thr Lys Gly Lys Thr Val Pro Ile Asp Asp Ser 
1               5                   10                  15      


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


Gln Gly Asn Leu Lys Lys Ala Leu Val Asn Val Glu Trp Asn Ile Cys 
        35                  40                  45              


Gln Asp Cys Lys Thr Asp Asn Lys Val Lys Asp Lys Ala Glu Glu Glu 
    50                  55                  60                  


Thr Glu Glu Lys Pro Ser Val Trp Leu Cys Leu Lys Cys Gly His Gln 
65                  70                  75                  80  


Gly Cys Gly Arg Asn Ser Gln Glu Gln His Ala Leu Lys His Tyr Leu 
                85                  90                  95      


Thr Pro Arg Ser Glu Pro His Cys Leu Val Leu Ser Leu Asp Asn Trp 
            100                 105                 110         


Ser Val Trp Cys Tyr Val Cys Asp Asn Glu Val Gln Tyr Cys Ser Ser 
        115                 120                 125             


Asn Gln Leu Gly Gln Val Val Asp Tyr Val Arg Lys Gln Ala Ser Ile 
    130                 135                 140                 


Thr Thr Pro Lys Pro Ala Glu Lys Asp Asn Gly Asn Ile Glu Leu Glu 
145                 150                 155                 160 


Asn Lys Lys Leu Glu Lys Glu Ser Lys Asn Glu Gln Glu Arg Glu Lys 
                165                 170                 175     


Lys Glu Asn Met Ala Lys Glu Asn Pro Pro Met Asn Ser Pro Cys Gln 
            180                 185                 190         


Ile Thr Val Lys Gly Leu Ser Asn Leu Gly Asn Thr Cys Phe Phe Asn 
        195                 200                 205             


Ala Val Met Gln Asn Leu Ser Gln Thr Pro Val Leu Arg Glu Leu Leu 
    210                 215                 220                 


Lys Glu Val Lys Met Ser Gly Thr Ile Val Lys Ile Glu Pro Pro Asp 
225                 230                 235                 240 


Leu Ala Leu Thr Glu Pro Leu Glu Ile Asn Leu Glu Pro Pro Gly Pro 
                245                 250                 255     


Leu Thr Leu Ala Met Ser Gln Phe Leu Asn Glu Met Gln Glu Thr Lys 
            260                 265                 270         


Lys Gly Val Val Thr Pro Lys Glu Leu Phe Ser Gln Val Cys Lys Lys 
        275                 280                 285             


Ala Val Arg Phe Lys Gly Tyr Gln Gln Gln Asp Ser Gln Glu Leu Leu 
    290                 295                 300                 


Arg Tyr Leu Leu Asp Gly Met Arg Ala Glu Glu His Gln Arg Val Ser 
305                 310                 315                 320 


Lys Gly Ile Leu Lys Ala Phe Gly Asn Ser Thr Glu Lys Leu Asp Glu 
                325                 330                 335     


Glu Leu Lys Asn Lys Val Lys Asp Tyr Glu Lys Lys Lys Ser Met Pro 
            340                 345                 350         


Ser Phe Val Asp Arg Ile Phe Gly Gly Glu Leu Thr Ser Met Ile Met 
        355                 360                 365             


Cys Asp Gln Cys Arg Thr Val Ser Leu Val His Glu Ser Phe Leu Asp 
    370                 375                 380                 


Leu Ser Leu Pro Val Leu Asp Asp Gln Ser Gly Lys Lys Ser Val Asn 
385                 390                 395                 400 


Asp Lys Asn Leu Lys Lys Thr Val Glu Asp Glu Asp Gln Asp Ser Glu 
                405                 410                 415     


Glu Glu Lys Asp Asn Asp Ser Tyr Ile Lys Glu Arg Ser Asp Ile Pro 
            420                 425                 430         


Ser Gly Thr Ser Lys His Leu Gln Lys Lys Ala Lys Lys Gln Ala Lys 
        435                 440                 445             


Lys Gln Ala Lys Asn Gln Arg Arg Gln Gln Lys Ile Gln Gly Lys Val 
    450                 455                 460                 


Leu His Leu Asn Asp Ile Cys Thr Ile Asp His Pro Glu Asp Ser Glu 
465                 470                 475                 480 


Tyr Glu Ala Glu Met Ser Leu Gln Gly Glu Val Asn Ile Lys Ser Asn 
                485                 490                 495     


His Ile Ser Gln Glu Gly Val Met His Lys Glu Tyr Cys Val Asn Gln 
            500                 505                 510         


Lys Asp Leu Asn Gly Gln Ala Lys Met Ile Glu Ser Val Thr Asp Asn 
        515                 520                 525             


Gln Lys Ser Thr Glu Glu Val Asp Met Lys Asn Ile Asn Met Asp Asn 
    530                 535                 540                 


Asp Leu Glu Val Leu Thr Ser Ser Pro Thr Arg Asn Leu Asn Gly Ala 
545                 550                 555                 560 


Tyr Leu Thr Glu Gly Ser Asn Gly Glu Val Asp Ile Ser Asn Gly Phe 
                565                 570                 575     


Lys Asn Leu Asn Leu Asn Ala Ala Leu His Pro Asp Glu Ile Asn Ile 
            580                 585                 590         


Glu Ile Leu Asn Asp Ser His Thr Pro Gly Thr Lys Val Tyr Glu Val 
        595                 600                 605             


Val Asn Glu Asp Pro Glu Thr Ala Phe Cys Thr Leu Ala Asn Arg Glu 
    610                 615                 620                 


Val Phe Asn Thr Asp Glu Cys Ser Ile Gln His Cys Leu Tyr Gln Phe 
625                 630                 635                 640 


Thr Arg Asn Glu Lys Leu Arg Asp Ala Asn Lys Leu Leu Cys Glu Val 
                645                 650                 655     


Cys Thr Arg Arg Gln Cys Asn Gly Pro Lys Ala Asn Ile Lys Gly Glu 
            660                 665                 670         


Arg Lys His Val Tyr Thr Asn Ala Lys Lys Gln Met Leu Ile Ser Leu 
        675                 680                 685             


Ala Pro Pro Val Leu Thr Leu His Leu Lys Arg Phe Gln Gln Ala Gly 
    690                 695                 700                 


Phe Asn Leu Arg Lys Val Asn Lys His Ile Lys Phe Pro Glu Ile Leu 
705                 710                 715                 720 


Asp Leu Ala Pro Phe Cys Thr Leu Lys Cys Lys Asn Val Ala Glu Glu 
                725                 730                 735     


Asn Thr Arg Val Leu Tyr Ser Leu Tyr Gly Val Val Glu His Ser Gly 
            740                 745                 750         


Thr Met Arg Ser Gly His Tyr Thr Ala Tyr Ala Lys Ala Arg Thr Ala 
        755                 760                 765             


Asn Ser His Leu Ser Asn Leu Val Leu His Gly Asp Ile Pro Gln Asp 
    770                 775                 780                 


Phe Glu Met Glu Ser Lys Gly Gln Trp Phe His Ile Ser Asp Thr His 
785                 790                 795                 800 


Val Gln Ala Val Pro Thr Thr Lys Val Leu Asn Ser Gln Ala Tyr Leu 
                805                 810                 815     


Leu Phe Tyr Glu Arg Ile Leu 
            820             


<210>  5
<211>  822
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  USP16 protein variant

<400>  5

Met Gly Lys Lys Arg Thr Lys Gly Lys Thr Val Pro Ile Asp Asp Ser 
1               5                   10                  15      


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


Gln Gly Asn Leu Lys Lys Ala Leu Val Asn Val Glu Trp Asn Ile Cys 
        35                  40                  45              


Gln Asp Cys Lys Thr Asp Asn Lys Val Lys Asp Lys Ala Glu Glu Glu 
    50                  55                  60                  


Thr Glu Glu Lys Pro Ser Val Trp Leu Cys Leu Lys Cys Gly His Gln 
65                  70                  75                  80  


Gly Cys Gly Arg Asn Ser Gln Glu Gln His Ala Leu Lys His Tyr Leu 
                85                  90                  95      


Thr Pro Arg Ser Glu Pro His Cys Leu Val Leu Ser Leu Asp Asn Trp 
            100                 105                 110         


Ser Val Trp Cys Tyr Val Cys Asp Asn Glu Val Gln Tyr Cys Ser Ser 
        115                 120                 125             


Asn Gln Leu Gly Gln Val Val Asp Tyr Val Arg Lys Gln Ala Ser Ile 
    130                 135                 140                 


Thr Thr Pro Lys Pro Glu Lys Asp Asn Gly Asn Ile Glu Leu Glu Asn 
145                 150                 155                 160 


Lys Lys Leu Glu Lys Glu Ser Lys Asn Glu Gln Glu Arg Glu Lys Lys 
                165                 170                 175     


Glu Asn Met Ala Lys Glu Asn Pro Pro Met Asn Ser Pro Cys Gln Ile 
            180                 185                 190         


Thr Val Lys Gly Leu Ser Asn Leu Gly Asn Thr Cys Phe Phe Asn Ala 
        195                 200                 205             


Val Met Gln Asn Leu Ser Gln Thr Pro Val Leu Arg Glu Leu Leu Lys 
    210                 215                 220                 


Glu Val Lys Met Ser Gly Thr Ile Val Lys Ile Glu Pro Pro Asp Leu 
225                 230                 235                 240 


Ala Leu Thr Glu Pro Leu Glu Ile Asn Leu Glu Pro Pro Gly Pro Leu 
                245                 250                 255     


Thr Leu Ala Met Ser Gln Phe Leu Asn Glu Met Gln Glu Thr Lys Lys 
            260                 265                 270         


Gly Val Val Thr Pro Lys Glu Leu Phe Ser Gln Val Cys Lys Lys Ala 
        275                 280                 285             


Val Arg Phe Lys Gly Tyr Gln Gln Gln Asp Ser Gln Glu Leu Leu Arg 
    290                 295                 300                 


Tyr Leu Leu Asp Gly Met Arg Ala Glu Glu His Gln Arg Val Ser Lys 
305                 310                 315                 320 


Gly Ile Leu Lys Ala Phe Gly Asn Ser Thr Glu Lys Leu Asp Glu Glu 
                325                 330                 335     


Leu Lys Asn Lys Val Lys Asp Tyr Glu Lys Lys Lys Ser Met Pro Ser 
            340                 345                 350         


Phe Val Asp Arg Ile Phe Gly Gly Glu Leu Thr Ser Met Ile Met Cys 
        355                 360                 365             


Asp Gln Cys Arg Thr Val Ser Leu Val His Glu Ser Phe Leu Asp Leu 
    370                 375                 380                 


Ser Leu Pro Val Leu Asp Asp Gln Ser Gly Lys Lys Ser Val Asn Asp 
385                 390                 395                 400 


Lys Asn Leu Lys Lys Thr Val Glu Asp Glu Asp Gln Asp Ser Glu Glu 
                405                 410                 415     


Glu Lys Asp Asn Asp Ser Tyr Ile Lys Glu Arg Ser Asp Ile Pro Ser 
            420                 425                 430         


Gly Thr Ser Lys His Leu Gln Lys Lys Ala Lys Lys Gln Ala Lys Lys 
        435                 440                 445             


Gln Ala Lys Asn Gln Arg Arg Gln Gln Lys Ile Gln Gly Lys Val Leu 
    450                 455                 460                 


His Leu Asn Asp Ile Cys Thr Ile Asp His Pro Glu Asp Ser Glu Tyr 
465                 470                 475                 480 


Glu Ala Glu Met Ser Leu Gln Gly Glu Val Asn Ile Lys Ser Asn His 
                485                 490                 495     


Ile Ser Gln Glu Gly Val Met His Lys Glu Tyr Cys Val Asn Gln Lys 
            500                 505                 510         


Asp Leu Asn Gly Gln Ala Lys Met Ile Glu Ser Val Thr Asp Asn Gln 
        515                 520                 525             


Lys Ser Thr Glu Glu Val Asp Met Lys Asn Ile Asn Met Asp Asn Asp 
    530                 535                 540                 


Leu Glu Val Leu Thr Ser Ser Pro Thr Arg Asn Leu Asn Gly Ala Tyr 
545                 550                 555                 560 


Leu Thr Glu Gly Ser Asn Gly Glu Val Asp Ile Ser Asn Gly Phe Lys 
                565                 570                 575     


Asn Leu Asn Leu Asn Ala Ala Leu His Pro Asp Glu Ile Asn Ile Glu 
            580                 585                 590         


Ile Leu Asn Asp Ser His Thr Pro Gly Thr Lys Val Tyr Glu Val Val 
        595                 600                 605             


Asn Glu Asp Pro Glu Thr Ala Phe Cys Thr Leu Ala Asn Arg Glu Val 
    610                 615                 620                 


Phe Asn Thr Asp Glu Cys Ser Ile Gln His Cys Leu Tyr Gln Phe Thr 
625                 630                 635                 640 


Arg Asn Glu Lys Leu Arg Asp Ala Asn Lys Leu Leu Cys Glu Val Cys 
                645                 650                 655     


Thr Arg Arg Gln Cys Asn Gly Pro Lys Ala Asn Ile Lys Gly Glu Arg 
            660                 665                 670         


Lys His Val Tyr Thr Asn Ala Lys Lys Gln Met Leu Ile Ser Leu Ala 
        675                 680                 685             


Pro Pro Val Leu Thr Leu His Leu Lys Arg Phe Gln Gln Ala Gly Phe 
    690                 695                 700                 


Asn Leu Arg Lys Val Asn Lys His Ile Lys Phe Pro Glu Ile Leu Asp 
705                 710                 715                 720 


Leu Ala Pro Phe Cys Thr Leu Lys Cys Lys Asn Val Ala Glu Glu Asn 
                725                 730                 735     


Thr Arg Val Leu Tyr Ser Leu Tyr Gly Val Val Glu His Ser Gly Thr 
            740                 745                 750         


Met Arg Ser Gly His Tyr Thr Ala Tyr Ala Lys Ala Arg Thr Ala Asn 
        755                 760                 765             


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


Glu Met Glu Ser Lys Gly Gln Trp Phe His Ile Ser Asp Thr His Val 
785                 790                 795                 800 


Gln Ala Val Pro Thr Thr Lys Val Leu Asn Ser Gln Ala Tyr Leu Leu 
                805                 810                 815     


Phe Tyr Glu Arg Ile Leu 
            820         


<210>  6
<211>  823
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  USP16 protein variant

<400>  6

Met Gly Lys Lys Arg Thr Lys Gly Lys Thr Val Pro Ile Asp Asp Ser 
1               5                   10                  15      


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


Gln Gly Asn Leu Lys Lys Ala Leu Val Asn Val Glu Trp Asn Ile Cys 
        35                  40                  45              


Gln Asp Cys Lys Thr Asp Asn Lys Val Lys Asp Lys Ala Glu Glu Glu 
    50                  55                  60                  


Thr Glu Glu Lys Pro Ser Val Trp Leu Cys Leu Lys Cys Gly His Gln 
65                  70                  75                  80  


Gly Cys Gly Arg Asn Ser Gln Glu Gln His Ala Leu Lys His Tyr Leu 
                85                  90                  95      


Thr Pro Arg Ser Glu Pro His Cys Leu Val Leu Ser Leu Asp Asn Trp 
            100                 105                 110         


Ser Val Trp Cys Tyr Val Cys Asp Asn Glu Val Gln Tyr Cys Ser Ser 
        115                 120                 125             


Asn Gln Leu Gly Gln Val Val Asp Tyr Val Arg Lys Gln Ala Ser Ile 
    130                 135                 140                 


Thr Thr Pro Lys Pro Ala Glu Lys Asp Asn Gly Asn Ile Glu Leu Glu 
145                 150                 155                 160 


Asn Lys Lys Leu Glu Lys Glu Ser Lys Asn Glu Gln Glu Arg Glu Lys 
                165                 170                 175     


Lys Glu Asn Met Ala Lys Glu Asn Pro Pro Met Asn Ser Pro Cys Gln 
            180                 185                 190         


Ile Thr Val Lys Gly Leu Ser Asn Leu Gly Asn Thr Cys Phe Phe Asn 
        195                 200                 205             


Ala Val Met Gln Asn Leu Ser Gln Thr Pro Val Leu Arg Glu Leu Leu 
    210                 215                 220                 


Lys Glu Val Lys Met Ser Gly Thr Ile Val Lys Ile Glu Pro Pro Asp 
225                 230                 235                 240 


Leu Ala Leu Thr Glu Pro Leu Glu Ile Asn Leu Glu Pro Pro Gly Pro 
                245                 250                 255     


Leu Thr Leu Ala Met Ser Gln Phe Leu Asn Glu Met Gln Glu Thr Lys 
            260                 265                 270         


Lys Gly Val Val Thr Pro Lys Glu Leu Phe Ser Gln Val Cys Lys Lys 
        275                 280                 285             


Ala Val Arg Phe Lys Gly Tyr Gln Gln Gln Asp Ser Gln Glu Leu Leu 
    290                 295                 300                 


Arg Tyr Leu Leu Asp Gly Met Arg Ala Glu Glu His Gln Arg Val Ser 
305                 310                 315                 320 


Lys Gly Ile Leu Lys Ala Phe Gly Asn Ser Thr Glu Lys Leu Asp Glu 
                325                 330                 335     


Glu Leu Lys Asn Lys Val Lys Asp Tyr Glu Lys Lys Lys Ser Met Pro 
            340                 345                 350         


Ser Phe Val Asp Arg Ile Phe Gly Gly Glu Leu Thr Ser Met Ile Met 
        355                 360                 365             


Cys Asp Gln Cys Arg Thr Val Ser Leu Val His Glu Ser Phe Leu Asp 
    370                 375                 380                 


Leu Ser Leu Pro Val Leu Asp Asp Gln Ser Gly Lys Lys Ser Val Asn 
385                 390                 395                 400 


Asp Lys Asn Leu Lys Lys Thr Val Glu Asp Glu Asp Gln Asp Ser Glu 
                405                 410                 415     


Glu Glu Lys Asp Asn Asp Ser Tyr Ile Lys Glu Arg Ser Asp Ile Pro 
            420                 425                 430         


Ser Gly Thr Ser Lys His Leu Gln Lys Lys Ala Lys Lys Gln Ala Lys 
        435                 440                 445             


Lys Gln Ala Lys Asn Gln Arg Arg Gln Gln Lys Ile Gln Gly Lys Val 
    450                 455                 460                 


Leu His Leu Asn Asp Ile Cys Thr Ile Asp His Pro Glu Asp Ser Glu 
465                 470                 475                 480 


Tyr Glu Ala Glu Met Ser Leu Gln Gly Glu Val Asn Ile Lys Ser Asn 
                485                 490                 495     


His Ile Ser Gln Glu Gly Val Met His Lys Glu Tyr Cys Val Asn Gln 
            500                 505                 510         


Lys Asp Leu Asn Gly Gln Ala Lys Met Ile Glu Ser Val Thr Asp Asn 
        515                 520                 525             


Gln Lys Ser Thr Glu Glu Val Asp Met Lys Asn Ile Asn Met Asp Asn 
    530                 535                 540                 


Asp Leu Glu Val Leu Thr Ser Ser Pro Thr Arg Asn Leu Asn Gly Ala 
545                 550                 555                 560 


Tyr Leu Thr Glu Gly Ser Asn Gly Glu Val Asp Ile Ser Asn Gly Phe 
                565                 570                 575     


Lys Asn Leu Asn Leu Asn Ala Ala Leu His Pro Asp Glu Ile Asn Ile 
            580                 585                 590         


Glu Ile Leu Asn Asp Ser His Thr Pro Gly Thr Lys Val Tyr Glu Val 
        595                 600                 605             


Val Asn Glu Asp Pro Glu Thr Ala Phe Cys Thr Leu Ala Asn Arg Glu 
    610                 615                 620                 


Val Phe Asn Thr Asp Glu Cys Ser Ile Gln His Cys Leu Tyr Gln Phe 
625                 630                 635                 640 


Thr Arg Asn Glu Lys Leu Arg Asp Ala Asn Lys Leu Leu Cys Glu Val 
                645                 650                 655     


Cys Thr Arg Arg Gln Cys Asn Gly Pro Lys Ala Asn Ile Lys Gly Glu 
            660                 665                 670         


Arg Lys His Val Tyr Thr Asn Ala Lys Lys Gln Met Leu Ile Ser Leu 
        675                 680                 685             


Ala Pro Pro Val Leu Thr Leu His Leu Lys Arg Phe Gln Gln Ala Gly 
    690                 695                 700                 


Phe Asn Leu Arg Lys Val Asn Lys His Ile Lys Phe Pro Glu Ile Leu 
705                 710                 715                 720 


Asp Leu Ala Pro Phe Cys Thr Leu Lys Cys Lys Asn Val Ala Glu Glu 
                725                 730                 735     


Asn Thr Arg Val Leu Tyr Ser Leu Tyr Gly Val Val Glu His Ser Gly 
            740                 745                 750         


Thr Met Arg Ser Gly His Tyr Thr Ala Tyr Ala Lys Ala Arg Thr Ala 
        755                 760                 765             


Asn Ser His Leu Ser Asn Leu Val Leu His Gly Asp Ile Pro Gln Asp 
    770                 775                 780                 


Phe Glu Met Glu Ser Lys Gly Gln Trp Phe His Ile Ser Asp Thr His 
785                 790                 795                 800 


Val Gln Ala Val Pro Thr Thr Lys Val Leu Asn Ser Gln Ala Tyr Leu 
                805                 810                 815     


Leu Phe Tyr Glu Arg Ile Leu 
            820             


<210>  7
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  USP16 protein variant

<400>  7

Met Gly Lys Lys Arg Thr Lys Gly Lys Thr Val Pro Ile Asp Asp Ser 
1               5                   10                  15      


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


Gln Gly Asn Leu Lys Lys Ala Leu Val Asn Val Glu Trp Asn Ile Cys 
        35                  40                  45              


Gln Asp Cys Lys Thr Asp Asn Lys Val Lys Asp Lys Ala Glu Glu Glu 
    50                  55                  60                  


Thr Glu Glu Lys Pro Ser Val Trp Leu Cys Leu Lys Cys Gly His Gln 
65                  70                  75                  80  


Gly Cys Gly Arg Asn Ser Gln Glu Gln His Ala Leu Lys His Tyr Leu 
                85                  90                  95      


Thr Pro Arg Ser Glu Pro His Cys Leu Val Leu 
            100                 105         


<210>  8
<211>  21
<212>  DNA
<213>  Unknown

<220>
<223>  shRNA sequence shUSP16 1

<400>  8
gactgtaaga ctgacaataa a                                                 21


<210>  9
<211>  20
<212>  DNA
<213>  Unknown

<220>
<223>  shRNA sequence shUSP16 2

<400>  9
tatatcagtt cacccgtaat                                                   20


<210>  10
<211>  20
<212>  RNA
<213>  Unknown

<220>
<223>  sgRNA gUSP16 1

<400>  10
uggcgucaga uagugcuuca                                                   20


<210>  11
<211>  20
<212>  RNA
<213>  Unknown

<220>
<223>  sgRNA gRNA-A

<400>  11
gugugcagac acauuagaaa                                                   20


<210>  12
<211>  20
<212>  RNA
<213>  Unknown

<220>
<223>  sgRNA gRNA-B

<400>  12
uauugucagu cuuacagucu                                                   20


<210>  13
<211>  20
<212>  RNA
<213>  Unknown

<220>
<223>  sgRNA gRNA-C

<400>  13
guuuggcugu gucuuaaaug                                                   20


