                         SEQUENCE LISTING

<110>  The Board of Trustees of the Leland Stanford Junior 
       University
       Feng, Yanan
       Xu, Weijing
       Deng, Ning
       Cohen, Stanley N.
 
<120>  MICRO-VESICLES COMPRISING CARGO PRODRUG RNA AND METHODS OF USING 
       THE SAME

<130>  STAN-1764WO

<140>  PCT/US2021/047262
<141>  2021-08-24

<150>  US 63/071,018
<151>  2020-08-27

<160>  13    

<170>  PatentIn version 3.5

<210>  1
<211>  390
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Ala Val Ser Glu Ser Gln Leu Lys Lys Met Val Ser Lys Tyr Lys 
1               5                   10                  15      


Tyr Arg Asp Leu Thr Val Arg Glu Thr Val Asn Val Ile Thr Leu Tyr 
            20                  25                  30          


Lys Asp Leu Lys Pro Val Leu Asp Ser Tyr Val Phe Asn Asp Gly Ser 
        35                  40                  45              


Ser Arg Glu Leu Met Asn Leu Thr Gly Thr Ile Pro Val Pro Tyr Arg 
    50                  55                  60                  


Gly Asn Thr Tyr Asn Ile Pro Ile Cys Leu Trp Leu Leu Asp Thr Tyr 
65                  70                  75                  80  


Pro Tyr Asn Pro Pro Ile Cys Phe Val Lys Pro Thr Ser Ser Met Thr 
                85                  90                  95      


Ile Lys Thr Gly Lys His Val Asp Ala Asn Gly Lys Ile Tyr Leu Pro 
            100                 105                 110         


Tyr Leu His Glu Trp Lys His Pro Gln Ser Asp Leu Leu Gly Leu Ile 
        115                 120                 125             


Gln Val Met Ile Val Val Phe Gly Asp Glu Pro Pro Val Phe Ser Arg 
    130                 135                 140                 


Pro Ile Ser Ala Ser Tyr Pro Pro Tyr Gln Ala Thr Gly Pro Pro Asn 
145                 150                 155                 160 


Thr Ser Tyr Met Pro Gly Met Pro Gly Gly Ile Ser Pro Tyr Pro Ser 
                165                 170                 175     


Gly Tyr Pro Pro Asn Pro Ser Gly Tyr Pro Gly Cys Pro Tyr Pro Pro 
            180                 185                 190         


Gly Gly Pro Tyr Pro Ala Thr Thr Ser Ser Gln Tyr Pro Ser Gln Pro 
        195                 200                 205             


Pro Val Thr Thr Val Gly Pro Ser Arg Asp Gly Thr Ile Ser Glu Asp 
    210                 215                 220                 


Thr Ile Arg Ala Ser Leu Ile Ser Ala Val Ser Asp Lys Leu Arg Trp 
225                 230                 235                 240 


Arg Met Lys Glu Glu Met Asp Arg Ala Gln Ala Glu Leu Asn Ala Leu 
                245                 250                 255     


Lys Arg Thr Glu Glu Asp Leu Lys Lys Gly His Gln Lys Leu Glu Glu 
            260                 265                 270         


Met Val Thr Arg Leu Asp Gln Glu Val Ala Glu Val Asp Lys Asn Ile 
        275                 280                 285             


Glu Leu Leu Lys Lys Lys Asp Glu Glu Leu Ser Ser Ala Leu Glu Lys 
    290                 295                 300                 


Met Glu Asn Gln Ser Glu Asn Asn Asp Ile Asp Glu Val Ile Ile Pro 
305                 310                 315                 320 


Thr Ala Pro Leu Tyr Lys Gln Ile Leu Asn Leu Tyr Ala Glu Glu Asn 
                325                 330                 335     


Ala Ile Glu Asp Thr Ile Phe Tyr Leu Gly Glu Ala Leu Arg Arg Gly 
            340                 345                 350         


Val Ile Asp Leu Asp Val Phe Leu Lys His Val Arg Leu Leu Ser Arg 
        355                 360                 365             


Lys Gln Phe Gln Leu Arg Ala Leu Met Gln Lys Ala Arg Lys Thr Ala 
    370                 375                 380                 


Gly Leu Ser Asp Leu Tyr 
385                 390 


<210>  2
<211>  391
<212>  PRT
<213>  Mus musculus

<400>  2

Met Ala Val Ser Glu Ser Gln Leu Lys Lys Met Met Ser Lys Tyr Lys 
1               5                   10                  15      


Tyr Arg Asp Leu Thr Val Arg Gln Thr Val Asn Val Ile Ala Met Tyr 
            20                  25                  30          


Lys Asp Leu Lys Pro Val Leu Asp Ser Tyr Val Phe Asn Asp Gly Ser 
        35                  40                  45              


Ser Arg Glu Leu Val Asn Leu Thr Gly Thr Ile Pro Val Arg Tyr Arg 
    50                  55                  60                  


Gly Asn Ile Tyr Asn Ile Pro Ile Cys Leu Trp Leu Leu Asp Thr Tyr 
65                  70                  75                  80  


Pro Tyr Asn Pro Pro Ile Cys Phe Val Lys Pro Thr Ser Ser Met Thr 
                85                  90                  95      


Ile Lys Thr Gly Lys His Val Asp Ala Asn Gly Lys Ile Tyr Leu Pro 
            100                 105                 110         


Tyr Leu His Asp Trp Lys His Pro Arg Ser Glu Leu Leu Glu Leu Ile 
        115                 120                 125             


Gln Ile Met Ile Val Ile Phe Gly Glu Glu Pro Pro Val Phe Ser Arg 
    130                 135                 140                 


Pro Thr Val Ser Ala Ser Tyr Pro Pro Tyr Thr Ala Thr Gly Pro Pro 
145                 150                 155                 160 


Asn Thr Ser Tyr Met Pro Gly Met Pro Ser Gly Ile Ser Ala Tyr Pro 
                165                 170                 175     


Ser Gly Tyr Pro Pro Asn Pro Ser Gly Tyr Pro Gly Cys Pro Tyr Pro 
            180                 185                 190         


Pro Ala Gly Pro Tyr Pro Ala Thr Thr Ser Ser Gln Tyr Pro Ser Gln 
        195                 200                 205             


Pro Pro Val Thr Thr Val Gly Pro Ser Arg Asp Gly Thr Ile Ser Glu 
    210                 215                 220                 


Asp Thr Ile Arg Ala Ser Leu Ile Ser Ala Val Ser Asp Lys Leu Arg 
225                 230                 235                 240 


Trp Arg Met Lys Glu Glu Met Asp Gly Ala Gln Ala Glu Leu Asn Ala 
                245                 250                 255     


Leu Lys Arg Thr Glu Glu Asp Leu Lys Lys Gly His Gln Lys Leu Glu 
            260                 265                 270         


Glu Met Val Thr Arg Leu Asp Gln Glu Val Ala Glu Val Asp Lys Asn 
        275                 280                 285             


Ile Glu Leu Leu Lys Lys Lys Asp Glu Glu Leu Ser Ser Ala Leu Glu 
    290                 295                 300                 


Lys Met Glu Asn Gln Ser Glu Asn Asn Asp Ile Asp Glu Val Ile Ile 
305                 310                 315                 320 


Pro Thr Ala Pro Leu Tyr Lys Gln Ile Leu Asn Leu Tyr Ala Glu Glu 
                325                 330                 335     


Asn Ala Ile Glu Asp Thr Ile Phe Tyr Leu Gly Glu Ala Leu Arg Arg 
            340                 345                 350         


Gly Val Ile Asp Leu Asp Val Phe Leu Lys His Val Arg Leu Leu Ser 
        355                 360                 365             


Arg Lys Gln Phe Gln Leu Arg Ala Leu Met Gln Lys Ala Arg Lys Thr 
    370                 375                 380                 


Ala Gly Leu Ser Asp Leu Tyr 
385                 390     


<210>  3
<211>  391
<212>  PRT
<213>  Rattus norvegicus

<400>  3

Met Ala Val Ser Glu Ser Gln Leu Lys Lys Met Met Ser Lys Tyr Lys 
1               5                   10                  15      


Tyr Arg Asp Leu Thr Val Arg Gln Thr Val Asn Val Ile Ala Met Tyr 
            20                  25                  30          


Lys Asp Leu Lys Pro Val Leu Asp Ser Tyr Val Phe Asn Asp Gly Ser 
        35                  40                  45              


Ser Arg Glu Leu Val Asn Leu Thr Gly Thr Ile Pro Val Arg Tyr Arg 
    50                  55                  60                  


Gly Asn Ile Tyr Asn Ile Pro Ile Cys Leu Trp Leu Leu Asp Thr Tyr 
65                  70                  75                  80  


Pro Tyr Asn Pro Pro Ile Cys Phe Val Lys Pro Thr Ser Ser Met Thr 
                85                  90                  95      


Ile Lys Thr Gly Lys His Val Asp Ala Asn Gly Lys Ile Tyr Leu Pro 
            100                 105                 110         


Tyr Leu His Asp Trp Lys His Pro Arg Ser Glu Leu Leu Glu Leu Ile 
        115                 120                 125             


Gln Ile Met Ile Val Ile Phe Gly Glu Glu Pro Pro Val Phe Ser Arg 
    130                 135                 140                 


Pro Thr Val Ser Ala Ser Tyr Pro Pro Tyr Thr Ala Ala Gly Pro Pro 
145                 150                 155                 160 


Asn Thr Ser Tyr Leu Pro Ser Met Pro Ser Gly Ile Ser Ala Tyr Pro 
                165                 170                 175     


Ser Gly Tyr Pro Pro Asn Pro Ser Gly Tyr Pro Gly Cys Pro Tyr Pro 
            180                 185                 190         


Pro Ala Gly Pro Tyr Pro Ala Thr Thr Ser Ser Gln Tyr Pro Ser Gln 
        195                 200                 205             


Pro Pro Val Thr Thr Ala Gly Pro Ser Arg Asp Gly Thr Ile Ser Glu 
    210                 215                 220                 


Asp Thr Ile Arg Ala Ser Leu Ile Ser Ala Val Ser Asp Lys Leu Arg 
225                 230                 235                 240 


Trp Arg Met Lys Glu Glu Met Asp Gly Ala Gln Ala Glu Leu Asn Ala 
                245                 250                 255     


Leu Lys Arg Thr Glu Glu Asp Leu Lys Lys Gly His Gln Lys Leu Glu 
            260                 265                 270         


Glu Met Val Thr Arg Leu Asp Gln Glu Val Ala Glu Val Asp Lys Asn 
        275                 280                 285             


Ile Glu Leu Leu Lys Lys Lys Asp Glu Glu Leu Ser Ser Ala Leu Glu 
    290                 295                 300                 


Lys Met Glu Asn Gln Ser Glu Asn Asn Asp Ile Asp Glu Val Ile Ile 
305                 310                 315                 320 


Pro Thr Ala Pro Leu Tyr Lys Gln Ile Leu Asn Leu Tyr Ala Glu Glu 
                325                 330                 335     


Asn Ala Ile Glu Asp Thr Ile Phe Tyr Leu Gly Glu Ala Leu Arg Arg 
            340                 345                 350         


Gly Val Ile Asp Leu Asp Val Phe Leu Lys His Val Arg Leu Leu Ser 
        355                 360                 365             


Arg Lys Gln Phe Gln Leu Arg Ala Leu Met Gln Lys Ala Arg Lys Thr 
    370                 375                 380                 


Ala Gly Leu Ser Asp Leu Tyr 
385                 390     


<210>  4
<211>  433
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Gly Arg Val Gln Leu Phe Glu Ile Ser Leu Ser His Gly Arg Val 
1               5                   10                  15      


Val Tyr Ser Pro Gly Glu Pro Leu Ala Gly Thr Val Arg Val Arg Leu 
            20                  25                  30          


Gly Ala Pro Leu Pro Phe Arg Ala Ile Arg Val Thr Cys Ile Gly Ser 
        35                  40                  45              


Cys Gly Val Ser Asn Lys Ala Asn Asp Thr Ala Trp Val Val Glu Glu 
    50                  55                  60                  


Gly Tyr Phe Asn Ser Ser Leu Ser Leu Ala Asp Lys Gly Ser Leu Pro 
65                  70                  75                  80  


Ala Gly Glu His Ser Phe Pro Phe Gln Phe Leu Leu Pro Ala Thr Ala 
                85                  90                  95      


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


Ala Ala Ile His Thr Pro Arg Phe Ser Lys Asp His Lys Cys Ser Leu 
        115                 120                 125             


Val Phe Tyr Ile Leu Ser Pro Leu Asn Leu Asn Ser Ile Pro Asp Ile 
    130                 135                 140                 


Glu Gln Pro Asn Val Ala Ser Ala Thr Lys Lys Phe Ser Tyr Lys Leu 
145                 150                 155                 160 


Val Lys Thr Gly Ser Val Val Leu Thr Ala Ser Thr Asp Leu Arg Gly 
                165                 170                 175     


Tyr Val Val Gly Gln Ala Leu Gln Leu His Ala Asp Val Glu Asn Gln 
            180                 185                 190         


Ser Gly Lys Asp Thr Ser Pro Val Val Ala Ser Leu Leu Gln Lys Val 
        195                 200                 205             


Ser Tyr Lys Ala Lys Arg Trp Ile His Asp Val Arg Thr Ile Ala Glu 
    210                 215                 220                 


Val Glu Gly Ala Gly Val Lys Ala Trp Arg Arg Ala Gln Trp His Glu 
225                 230                 235                 240 


Gln Ile Leu Val Pro Ala Leu Pro Gln Ser Ala Leu Pro Gly Cys Ser 
                245                 250                 255     


Leu Ile His Ile Asp Tyr Tyr Leu Gln Val Ser Leu Lys Ala Pro Glu 
            260                 265                 270         


Ala Thr Val Thr Leu Pro Val Phe Ile Gly Asn Ile Ala Val Asn His 
        275                 280                 285             


Ala Pro Val Ser Pro Arg Pro Gly Leu Gly Leu Pro Pro Gly Ala Pro 
    290                 295                 300                 


Pro Leu Val Val Pro Ser Ala Pro Pro Gln Glu Glu Ala Glu Ala Glu 
305                 310                 315                 320 


Ala Ala Ala Gly Gly Pro His Phe Leu Asp Pro Val Phe Leu Ser Thr 
                325                 330                 335     


Lys Ser His Ser Gln Arg Gln Pro Leu Leu Ala Thr Leu Ser Ser Val 
            340                 345                 350         


Pro Gly Ala Pro Glu Pro Cys Pro Gln Asp Gly Ser Pro Ala Ser His 
        355                 360                 365             


Pro Leu His Pro Pro Leu Cys Ile Ser Thr Gly Ala Thr Val Pro Tyr 
    370                 375                 380                 


Phe Ala Glu Gly Ser Gly Gly Pro Val Pro Thr Thr Ser Thr Leu Ile 
385                 390                 395                 400 


Leu Pro Pro Glu Tyr Ser Ser Trp Gly Tyr Pro Tyr Glu Ala Pro Pro 
                405                 410                 415     


Ser Tyr Glu Gln Ser Cys Gly Gly Val Glu Pro Ser Leu Thr Pro Glu 
            420                 425                 430         


Ser 
    


<210>  5
<211>  434
<212>  PRT
<213>  Mus musculus

<400>  5

Met Gly Arg Val Gln Leu Phe Glu Ile Arg Leu Ser Gln Gly Arg Val 
1               5                   10                  15      


Val Tyr Gly Pro Gly Glu Pro Leu Ala Gly Thr Val His Leu Arg Leu 
            20                  25                  30          


Gly Ala Pro Leu Pro Phe Arg Ala Ile Arg Val Thr Cys Met Gly Ser 
        35                  40                  45              


Cys Gly Val Ser Thr Lys Ala Asn Asp Gly Ala Trp Val Val Glu Glu 
    50                  55                  60                  


Ser Tyr Phe Asn Ser Ser Leu Ser Leu Ala Asp Lys Gly Ser Leu Pro 
65                  70                  75                  80  


Ala Gly Glu His Asn Phe Pro Phe Gln Phe Leu Leu Pro Ala Thr Ala 
                85                  90                  95      


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


Ala Ser Ile Asp Thr Pro Arg Phe Ser Lys Asp His Lys Cys Ser Leu 
        115                 120                 125             


Val Phe Tyr Ile Leu Ser Pro Leu Asn Leu Asn Ser Ile Pro Asp Ile 
    130                 135                 140                 


Glu Gln Pro Asn Val Ala Ser Thr Thr Lys Lys Phe Ser Tyr Lys Leu 
145                 150                 155                 160 


Val Lys Thr Gly Asn Val Val Leu Thr Ala Ser Thr Asp Leu Arg Gly 
                165                 170                 175     


Tyr Val Val Gly Gln Val Leu Arg Leu Gln Ala Asp Ile Glu Asn Gln 
            180                 185                 190         


Ser Gly Lys Asp Thr Ser Pro Val Val Ala Ser Leu Leu Gln Lys Val 
        195                 200                 205             


Ser Tyr Lys Ala Lys Arg Trp Ile Tyr Asp Val Arg Thr Ile Ala Glu 
    210                 215                 220                 


Val Glu Gly Thr Gly Val Lys Ala Trp Arg Arg Ala Gln Trp Gln Glu 
225                 230                 235                 240 


Gln Ile Leu Val Pro Ala Leu Pro Gln Ser Ala Leu Pro Gly Cys Ser 
                245                 250                 255     


Leu Ile His Ile Asp Tyr Tyr Leu Gln Val Ser Met Lys Ala Pro Glu 
            260                 265                 270         


Ala Thr Val Thr Leu Pro Leu Phe Val Gly Asn Ile Ala Val Asn Gln 
        275                 280                 285             


Thr Pro Leu Ser Pro Cys Pro Gly Arg Glu Ser Ser Pro Gly Thr Leu 
    290                 295                 300                 


Ser Leu Val Val Pro Ser Ala Pro Pro Gln Glu Glu Ala Glu Ala Val 
305                 310                 315                 320 


Ala Ser Gly Pro His Phe Ser Asp Pro Val Ser Leu Ser Thr Lys Ser 
                325                 330                 335     


His Ser Gln Gln Gln Pro Leu Ser Ala Pro Leu Gly Ser Val Ser Val 
            340                 345                 350         


Thr Thr Thr Glu Pro Trp Val Gln Val Gly Ser Pro Ala Arg His Ser 
        355                 360                 365             


Leu His Pro Pro Leu Cys Ile Ser Ile Gly Ala Thr Val Pro Tyr Phe 
    370                 375                 380                 


Ala Glu Gly Ser Ala Gly Pro Val Pro Thr Thr Ser Ala Leu Ile Leu 
385                 390                 395                 400 


Pro Pro Glu Tyr Ser Ser Trp Gly Tyr Pro Tyr Glu Ala Pro Pro Ser 
                405                 410                 415     


Tyr Glu Gln Ser Cys Gly Ala Ala Gly Thr Asp Leu Gly Leu Ile Pro 
            420                 425                 430         


Gly Ser 
        


<210>  6
<211>  433
<212>  PRT
<213>  Mus musculus

<400>  6

Met Gly Arg Val Gln Leu Phe Glu Ile Arg Leu Ser Gln Gly Arg Val 
1               5                   10                  15      


Val Tyr Gly Pro Gly Glu Pro Leu Ala Gly Thr Val His Leu Arg Leu 
            20                  25                  30          


Gly Ala Pro Leu Pro Phe Arg Ala Ile Arg Val Thr Cys Met Gly Ser 
        35                  40                  45              


Cys Gly Val Ser Thr Lys Ala Asn Asp Gly Ala Trp Val Val Glu Glu 
    50                  55                  60                  


Ser Tyr Phe Asn Ser Ser Leu Ser Leu Ala Asp Lys Gly Ser Leu Pro 
65                  70                  75                  80  


Ala Gly Glu His Asn Phe Pro Phe Gln Phe Leu Leu Pro Ala Thr Ala 
                85                  90                  95      


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


Ala Ser Ile Asp Thr Pro Arg Phe Ser Lys Asp His Lys Cys Ser Leu 
        115                 120                 125             


Val Phe Tyr Ile Leu Ser Pro Leu Asn Leu Asn Ser Ile Pro Asp Ile 
    130                 135                 140                 


Glu Gln Pro Asn Val Ala Ser Thr Thr Lys Lys Phe Ser Tyr Lys Leu 
145                 150                 155                 160 


Val Lys Thr Gly Asn Val Val Leu Thr Ala Ser Thr Asp Leu Arg Gly 
                165                 170                 175     


Tyr Val Val Gly Gln Val Leu Arg Leu Gln Ala Asp Ile Glu Asn Gln 
            180                 185                 190         


Ser Gly Lys Asp Thr Ser Pro Val Val Ala Ser Leu Leu Gln Val Ser 
        195                 200                 205             


Tyr Lys Ala Lys Arg Trp Ile Tyr Asp Val Arg Thr Ile Ala Glu Val 
    210                 215                 220                 


Glu Gly Thr Gly Val Lys Ala Trp Arg Arg Ala Gln Trp Gln Glu Gln 
225                 230                 235                 240 


Ile Leu Val Pro Ala Leu Pro Gln Ser Ala Leu Pro Gly Cys Ser Leu 
                245                 250                 255     


Ile His Ile Asp Tyr Tyr Leu Gln Val Ser Met Lys Ala Pro Glu Ala 
            260                 265                 270         


Thr Val Thr Leu Pro Leu Phe Val Gly Asn Ile Ala Val Asn Gln Thr 
        275                 280                 285             


Pro Leu Ser Pro Cys Pro Gly Arg Glu Ser Ser Pro Gly Thr Leu Ser 
    290                 295                 300                 


Leu Val Val Pro Ser Ala Pro Pro Gln Glu Glu Ala Glu Ala Val Ala 
305                 310                 315                 320 


Ser Gly Pro His Phe Ser Asp Pro Val Ser Leu Ser Thr Lys Ser His 
                325                 330                 335     


Ser Gln Gln Gln Pro Leu Ser Ala Pro Leu Gly Ser Val Ser Val Thr 
            340                 345                 350         


Thr Thr Glu Pro Trp Val Gln Val Gly Ser Pro Ala Arg His Ser Leu 
        355                 360                 365             


His Pro Pro Leu Cys Ile Ser Ile Gly Ala Thr Val Pro Tyr Phe Ala 
    370                 375                 380                 


Glu Gly Ser Ala Gly Pro Val Pro Thr Thr Ser Ala Leu Ile Leu Pro 
385                 390                 395                 400 


Pro Glu Tyr Ser Ser Trp Gly Tyr Pro Tyr Glu Ala Pro Pro Ser Tyr 
                405                 410                 415     


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


Ser 
    


<210>  7
<211>  7
<212>  PRT
<213>  Artificial sequence

<220>
<223>  synthetic sequence

<400>  7

Pro Lys Lys Lys Arg Lys Val 
1               5           


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

<220>
<223>  synthetic sequence

<400>  8

Met Asp Ser Leu Leu Met Asn Arg Arg Lys Phe Leu Tyr Gln Phe Lys 
1               5                   10                  15      


Asn Val Arg Trp Ala Lys Gly Arg Arg Glu Thr Tyr Leu Cys 
            20                  25                  30  


<210>  9
<211>  21
<212>  DNA
<213>  Artificial sequence

<220>
<223>  synthetic sequence

<400>  9
aggaagttct gttgaattaa a                                                 21


<210>  10
<211>  21
<212>  DNA
<213>  Artificial sequence

<220>
<223>  synthetic sequence

<400>  10
ctgcattgtg caaactttaa t                                                 21


<210>  11
<211>  19
<212>  RNA
<213>  Artificial sequence

<220>
<223>  synthetic sequence

<400>  11
gggcccugaa gaagggccc                                                    19


<210>  12
<211>  20
<212>  RNA
<213>  Artificial sequence

<220>
<223>  synthetic sequence

<400>  12
ucucaaccua accguugaga                                                   20


<210>  13
<211>  20
<212>  RNA
<213>  Artificial sequence

<220>
<223>  synthetic sequence

<400>  13
ggacuagcgg aggcuagucc                                                   20


