                         SEQUENCE LISTING

<110>  Evox Therapeutics Ltd
 
<120>  EXTRACELLULAR VESICLES FOR REPLACEMENT OF UREA CYCLE PROTEINS & 
       NUCLEIC ACIDS

<130>  Evox19 PCT

<150>  GB1818761.7
<151>  2018-11-16

<150>  GB1900197.3
<151>  2019-01-07

<160>  7     

<170>  PatentIn version 3.5

<210>  1
<211>  349
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PUF531

<400>  1

Gly Arg Ser Arg Leu Leu Glu Asp Phe Arg Asn Asn Arg Tyr Pro Asn 
1               5                   10                  15      


Leu Gln Leu Arg Glu Ile Ala Gly His Ile Met Glu Phe Ser Gln Asp 
            20                  25                  30          


Gln His Gly Ser Arg Phe Ile Glu Leu Lys Leu Glu Arg Ala Thr Pro 
        35                  40                  45              


Ala Glu Arg Gln Leu Val Phe Asn Glu Ile Leu Gln Ala Ala Tyr Gln 
    50                  55                  60                  


Leu Met Val Asp Val Phe Gly Asn Tyr Val Ile Gln Lys Phe Phe Glu 
65                  70                  75                  80  


Phe Gly Ser Leu Glu Gln Lys Leu Ala Leu Ala Glu Arg Ile Arg Gly 
                85                  90                  95      


His Val Leu Ser Leu Ala Leu Gln Met Tyr Gly Ser Arg Val Ile Glu 
            100                 105                 110         


Lys Ala Leu Glu Phe Ile Pro Ser Asp Gln Gln Asn Glu Met Val Arg 
        115                 120                 125             


Glu Leu Asp Gly His Val Leu Lys Cys Val Lys Asp Gln Asn Gly Asn 
    130                 135                 140                 


His Val Val Gln Lys Cys Ile Glu Cys Val Gln Pro Gln Ser Leu Gln 
145                 150                 155                 160 


Phe Ile Ile Asp Ala Phe Lys Gly Gln Val Phe Ala Leu Ser Thr His 
                165                 170                 175     


Pro Tyr Gly Ser Arg Val Ile Glu Arg Ile Leu Glu His Cys Leu Pro 
            180                 185                 190         


Asp Gln Thr Leu Pro Ile Leu Glu Glu Leu His Gln His Thr Glu Gln 
        195                 200                 205             


Leu Val Gln Asp Gln Tyr Gly Asn Tyr Val Ile Gln His Val Leu Glu 
    210                 215                 220                 


His Gly Arg Pro Glu Asp Lys Ser Lys Ile Val Ala Glu Ile Arg Gly 
225                 230                 235                 240 


Asn Val Leu Val Leu Ser Gln His Lys Phe Ala Ser Asn Val Val Glu 
                245                 250                 255     


Lys Cys Val Thr His Ala Ser Arg Thr Glu Arg Ala Val Leu Ile Asp 
            260                 265                 270         


Glu Val Cys Thr Met Asn Asp Gly Pro His Ser Ala Leu Tyr Thr Met 
        275                 280                 285             


Met Lys Asp Gln Tyr Ala Asn Tyr Val Val Gln Lys Met Ile Asp Val 
    290                 295                 300                 


Ala Glu Pro Gly Gln Arg Lys Ile Val Met His Lys Ile Arg Pro His 
305                 310                 315                 320 


Ile Ala Thr Leu Arg Lys Tyr Thr Tyr Gly Lys His Ile Leu Ala Lys 
                325                 330                 335     


Leu Glu Lys Tyr Tyr Met Lys Asn Gly Val Asp Leu Gly 
            340                 345                 


<210>  2
<211>  349
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PUF mRNA loc/PUFeng

<400>  2

Gly Arg Ser Arg Leu Leu Glu Asp Phe Arg Asn Asn Arg Tyr Pro Asn 
1               5                   10                  15      


Leu Gln Leu Arg Glu Ile Ala Gly His Ile Met Glu Phe Ser Gln Asp 
            20                  25                  30          


Gln His Gly Ser Arg Phe Ile Gln Leu Lys Leu Glu Arg Ala Thr Pro 
        35                  40                  45              


Ala Glu Arg Gln Leu Val Phe Asn Glu Ile Leu Gln Ala Ala Tyr Gln 
    50                  55                  60                  


Leu Met Val Asp Val Phe Gly Asn Tyr Val Ile Gln Lys Phe Phe Glu 
65                  70                  75                  80  


Phe Gly Ser Leu Glu Gln Lys Leu Ala Leu Ala Glu Arg Ile Arg Gly 
                85                  90                  95      


His Val Leu Ser Leu Ala Leu Gln Met Tyr Gly Cys Arg Val Ile Gln 
            100                 105                 110         


Lys Ala Leu Glu Phe Ile Pro Ser Asp Gln Gln Asn Glu Met Val Arg 
        115                 120                 125             


Glu Leu Asp Gly His Val Leu Lys Cys Val Lys Asp Gln Asn Gly Asn 
    130                 135                 140                 


His Val Val Gln Lys Cys Ile Glu Cys Val Gln Pro Gln Ser Leu Gln 
145                 150                 155                 160 


Phe Ile Ile Asp Ala Phe Lys Gly Gln Val Phe Ala Leu Ser Thr His 
                165                 170                 175     


Pro Tyr Gly Cys Arg Val Ile Gln Arg Ile Leu Glu His Cys Leu Pro 
            180                 185                 190         


Asp Gln Thr Leu Pro Ile Leu Glu Glu Leu His Gln His Thr Glu Gln 
        195                 200                 205             


Leu Val Gln Asp Gln Tyr Gly Ser Tyr Val Ile Glu His Val Leu Glu 
    210                 215                 220                 


His Gly Arg Pro Glu Asp Lys Ser Lys Ile Val Ala Glu Ile Arg Gly 
225                 230                 235                 240 


Asn Val Leu Val Leu Ser Gln His Lys Phe Ala Asn Asn Val Val Gln 
                245                 250                 255     


Lys Cys Val Thr His Ala Ser Arg Thr Glu Arg Ala Val Leu Ile Asp 
            260                 265                 270         


Glu Val Cys Thr Met Asn Asp Gly Pro His Ser Ala Leu Tyr Thr Met 
        275                 280                 285             


Met Lys Asp Gln Tyr Ala Asn Tyr Val Val Gln Lys Met Ile Asp Val 
    290                 295                 300                 


Ala Glu Pro Gly Gln Arg Lys Ile Val Met His Lys Ile Arg Pro His 
305                 310                 315                 320 


Ile Ala Thr Leu Arg Lys Tyr Thr Tyr Gly Lys His Ile Leu Ala Lys 
                325                 330                 335     


Leu Glu Lys Tyr Tyr Met Lys Asn Gly Val Asp Leu Gly 
            340                 345                 


<210>  3
<211>  644
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PUFx2

<400>  3

Gly Arg Ser Arg Leu Leu Glu Asp Phe Arg Asn Asn Arg Tyr Pro Asn 
1               5                   10                  15      


Leu Gln Leu Arg Glu Ile Ala Gly His Ile Met Glu Phe Ser Gln Asp 
            20                  25                  30          


Gln His Gly Ser Arg Phe Ile Gln Leu Lys Leu Glu Arg Ala Thr Pro 
        35                  40                  45              


Ala Glu Arg Gln Leu Val Phe Asn Glu Ile Leu Gln Ala Ala Tyr Gln 
    50                  55                  60                  


Leu Met Val Asp Val Phe Gly Asn Tyr Val Ile Gln Lys Phe Phe Glu 
65                  70                  75                  80  


Phe Gly Ser Leu Glu Gln Lys Leu Ala Leu Ala Glu Arg Ile Arg Gly 
                85                  90                  95      


His Val Leu Ser Leu Ala Leu Gln Met Tyr Gly Cys Arg Val Ile Gln 
            100                 105                 110         


Lys Ala Leu Glu Phe Ile Pro Ser Asp Gln Gln Asn Glu Met Val Arg 
        115                 120                 125             


Glu Leu Asp Gly His Val Leu Lys Cys Val Lys Asp Gln Asn Gly Asn 
    130                 135                 140                 


His Val Val Gln Lys Cys Ile Glu Cys Val Gln Pro Gln Ser Leu Gln 
145                 150                 155                 160 


Phe Ile Ile Asp Ala Phe Lys Gly Gln Val Phe Ala Leu Ser Thr His 
                165                 170                 175     


Pro Tyr Gly Cys Arg Val Ile Gln Arg Ile Leu Glu His Cys Leu Pro 
            180                 185                 190         


Asp Gln Thr Leu Pro Ile Leu Glu Glu Leu His Gln His Ile Met Glu 
        195                 200                 205             


Phe Ser Gln Asp Gln His Gly Ser Arg Phe Ile Gln Leu Lys Leu Glu 
    210                 215                 220                 


Arg Ala Thr Pro Ala Glu Arg Gln Leu Val Phe Asn Glu Ile Leu Gln 
225                 230                 235                 240 


Ala Ala Tyr Gln Leu Met Val Asp Val Phe Gly Asn Tyr Val Ile Gln 
                245                 250                 255     


Lys Phe Phe Glu Phe Gly Ser Leu Glu Gln Lys Leu Ala Leu Ala Glu 
            260                 265                 270         


Arg Ile Arg Gly His Val Leu Ser Leu Ala Leu Gln Met Tyr Gly Cys 
        275                 280                 285             


Arg Val Ile Gln Lys Ala Leu Glu Phe Ile Pro Ser Asp Gln Gln Asn 
    290                 295                 300                 


Glu Met Val Arg Glu Leu Asp Ser His Val Leu Lys Cys Val Lys Asp 
305                 310                 315                 320 


Gln Asn Gly Asn His Val Val Gln Lys Cys Ile Glu Cys Val Gln Pro 
                325                 330                 335     


Gln Ser Leu Gln Phe Ile Ile Asp Ala Phe Lys Gly Gln Val Phe Ala 
            340                 345                 350         


Leu Ser Thr His Pro Tyr Gly Cys Arg Val Ile Gln Arg Ile Leu Glu 
        355                 360                 365             


His Cys Leu Pro Asp Gln Thr Leu Pro Ile Leu Glu Glu Leu His Gln 
    370                 375                 380                 


His Thr Glu Gln Leu Val Gln Asp Gln Tyr Gly Asn Tyr Val Ile Gln 
385                 390                 395                 400 


His Val Leu Glu His Gly Arg Pro Glu Asp Lys Ser Lys Ile Val Ala 
                405                 410                 415     


Glu Ile Arg Gly Asn Val Leu Val Leu Ser Gln His Lys Phe Ala Ser 
            420                 425                 430         


Asn Val Val Glu Lys Cys Val Thr His Ala Ser Arg Thr Glu Arg Ala 
        435                 440                 445             


Val Leu Ile Asp Glu Val Cys Thr Met Asn Asp Gly Pro His Ser Ala 
    450                 455                 460                 


Leu Tyr Thr Met Met Lys Asp Gln Tyr Ala Asn Tyr Val Val Gln Lys 
465                 470                 475                 480 


Met Ile Asp Val Ala Glu Pro Gly Gln Arg Lys Ile Val Met His Glu 
                485                 490                 495     


Leu His Gln His Thr Glu Gln Leu Val Gln Asp Gln Tyr Gly Asn Tyr 
            500                 505                 510         


Val Ile Gln His Val Leu Glu His Gly Arg Pro Glu Asp Lys Ser Lys 
        515                 520                 525             


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


Phe Ala Ser Asn Val Val Glu Lys Cys Val Thr His Ala Ser Arg Thr 
545                 550                 555                 560 


Glu Arg Ala Val Leu Ile Asp Glu Val Cys Thr Met Asn Asp Gly Pro 
                565                 570                 575     


His Ser Ala Leu Tyr Thr Met Met Lys Asp Gln Tyr Ala Asn Tyr Val 
            580                 585                 590         


Val Gln Lys Met Ile Asp Val Ala Glu Pro Gly Gln Arg Lys Ile Val 
        595                 600                 605             


Met His Lys Ile Arg Pro His Ile Ala Thr Leu Arg Lys Tyr Thr Tyr 
    610                 615                 620                 


Gly Lys His Ile Leu Ala Lys Leu Glu Lys Tyr Tyr Met Lys Asn Gly 
625                 630                 635                 640 


Val Asp Leu Gly 
                


<210>  4
<211>  186
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Cas6

<400>  4

Asp His Tyr Leu Asp Ile Arg Leu Arg Pro Asp Pro Glu Phe Pro Pro 
1               5                   10                  15      


Ala Gln Leu Met Ser Val Leu Phe Gly Lys Leu His Gln Ala Leu Val 
            20                  25                  30          


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


Ser Arg Ser Arg Leu Gly Glu Arg Leu Arg Ile His Ala Ser Ala Asp 
    50                  55                  60                  


Asp Leu Arg Ala Leu Leu Ala Arg Pro Trp Leu Glu Gly Leu Arg Asp 
65                  70                  75                  80  


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


Arg Gln Val Ser Arg Val Gln Ala Lys Ser Asn Pro Glu Arg Leu Arg 
            100                 105                 110         


Arg Arg Leu Met Arg Arg His Asp Leu Ser Glu Glu Glu Ala Arg Lys 
        115                 120                 125             


Arg Ile Pro Asp Thr Val Ala Arg Ala Leu Asp Leu Pro Phe Val Thr 
    130                 135                 140                 


Leu Arg Ala Gln Ser Thr Gly Gln His Phe Arg Leu Phe Ile Arg His 
145                 150                 155                 160 


Gly Pro Leu Gln Val Thr Ala Glu Glu Gly Gly Phe Thr Cys Tyr Gly 
                165                 170                 175     


Leu Ser Lys Gly Gly Phe Val Pro Trp Phe 
            180                 185     


<210>  5
<211>  37
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  His aptamer

<400>  5

Gly Gly Gly Thr Ala Thr Ala Thr Thr Gly Gly Cys Gly Cys Cys Thr 
1               5                   10                  15      


Thr Cys Gly Thr Gly Gly Ala Ala Thr Gly Thr Cys Ala Gly Thr Gly 
            20                  25                  30          


Cys Cys Thr Gly Gly 
        35          


<210>  6
<211>  36
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TAT aptamer

<400>  6

Thr Gly Cys Thr Thr Cys Gly Ala Ala Cys Thr Ala Gly Gly Gly Cys 
1               5                   10                  15      


Ala Ala Ala Cys Gly Gly Cys Cys Ala Gly Cys Thr Ala Gly Cys Gly 
            20                  25                  30          


Ala Ala Gly Cys 
        35      


<210>  7
<211>  464
<212>  PRT
<213>  Homo sapiens

<400>  7

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


Val Asp Pro Ile Met Glu Lys Phe Asn Ala Ser Ile Ala Tyr Asp Arg 
            20                  25                  30          


His Leu Trp Glu Val Asp Val Gln Gly Ser Lys Ala Tyr Ser Arg Gly 
        35                  40                  45              


Leu Glu Lys Ala Gly Leu Leu Thr Lys Ala Glu Met Asp Gln Ile Leu 
    50                  55                  60                  


His Gly Leu Asp Lys Val Ala Glu Glu Trp Ala Gln Gly Thr Phe Lys 
65                  70                  75                  80  


Leu Asn Ser Asn Asp Glu Asp Ile His Thr Ala Asn Glu Arg Arg Leu 
                85                  90                  95      


Lys Glu Leu Ile Gly Ala Thr Ala Gly Lys Leu His Thr Gly Arg Ser 
            100                 105                 110         


Arg Asn Asp Gln Val Val Thr Asp Leu Arg Leu Trp Met Arg Gln Thr 
        115                 120                 125             


Cys Ser Thr Leu Ser Gly Leu Leu Trp Glu Leu Ile Arg Thr Met Val 
    130                 135                 140                 


Asp Arg Ala Glu Ala Glu Arg Asp Val Leu Phe Pro Gly Tyr Thr His 
145                 150                 155                 160 


Leu Gln Arg Ala Gln Pro Ile Arg Trp Ser His Trp Ile Leu Ser His 
                165                 170                 175     


Ala Val Ala Leu Thr Arg Asp Ser Glu Arg Leu Leu Glu Val Arg Lys 
            180                 185                 190         


Arg Ile Asn Val Leu Pro Leu Gly Ser Gly Ala Ile Ala Gly Asn Pro 
        195                 200                 205             


Leu Gly Val Asp Arg Glu Leu Leu Arg Ala Glu Leu Asn Phe Gly Ala 
    210                 215                 220                 


Ile Thr Leu Asn Ser Met Asp Ala Thr Ser Glu Arg Asp Phe Val Ala 
225                 230                 235                 240 


Glu Phe Leu Phe Trp Ala Ser Leu Cys Met Thr His Leu Ser Arg Met 
                245                 250                 255     


Ala Glu Asp Leu Ile Leu Tyr Cys Thr Lys Glu Phe Ser Phe Val Gln 
            260                 265                 270         


Leu Ser Asp Ala Tyr Ser Thr Gly Ser Ser Leu Met Pro Gln Lys Lys 
        275                 280                 285             


Asn Pro Asp Ser Leu Glu Leu Ile Arg Ser Lys Ala Gly Arg Val Phe 
    290                 295                 300                 


Gly Arg Cys Ala Gly Leu Leu Met Thr Leu Lys Gly Leu Pro Ser Thr 
305                 310                 315                 320 


Tyr Asn Lys Asp Leu Gln Glu Asp Lys Glu Ala Val Phe Glu Val Ser 
                325                 330                 335     


Asp Thr Met Ser Ala Val Leu Gln Val Ala Thr Gly Val Ile Ser Thr 
            340                 345                 350         


Leu Gln Ile His Gln Glu Asn Met Gly Gln Ala Leu Ser Pro Asp Met 
        355                 360                 365             


Leu Ala Thr Asp Leu Ala Tyr Tyr Leu Val Arg Lys Gly Met Pro Phe 
    370                 375                 380                 


Arg Gln Ala His Glu Ala Ser Gly Lys Ala Val Phe Met Ala Glu Thr 
385                 390                 395                 400 


Lys Gly Val Ala Leu Asn Gln Leu Ser Leu Gln Glu Leu Gln Thr Ile 
                405                 410                 415     


Ser Pro Leu Phe Ser Gly Asp Val Ile Cys Val Trp Asp Tyr Gly His 
            420                 425                 430         


Ser Val Glu Gln Tyr Gly Ala Leu Gly Gly Thr Ala Arg Ser Ser Val 
        435                 440                 445             


Asp Trp Gln Ile Arg Gln Val Arg Ala Leu Leu Gln Ala Gln Gln Ala 
    450                 455                 460                 


