                         SEQUENCE LISTING

<110>  Decibel Therapeutics, Inc.
 
<120>  METHODS AND COMPOSITIONS FOR REDUCING NUCLEIC ACID VECTOR-INDUCED
        TOXICITY IN THE INNER EAR

<130>  51124-092WO2

<150>  US 63/152,302
<151>  2021-02-22

<160>  7     

<170>  PatentIn version 3.5

<210>  1
<211>  354
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  1

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


Gly Asp His His Arg Gln Pro Gln Pro His His Leu Pro Gln Pro Pro 
            20                  25                  30          


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


Tyr Pro Pro Glu Leu Ser Leu Leu Asp Ser Thr Asp Pro Arg Ala Trp 
    50                  55                  60                  


Leu Ala Pro Thr Leu Gln Gly Ile Cys Thr Ala Arg Ala Ala Gln Tyr 
65                  70                  75                  80  


Leu Leu His Ser Pro Glu Leu Gly Ala Ser Glu Ala Ala Ala Pro Arg 
                85                  90                  95      


Asp Glu Val Asp Gly Arg Gly Glu Leu Val Arg Arg Ser Ser Gly Gly 
            100                 105                 110         


Ala Ser Ser Ser Lys Ser Pro Gly Pro Val Lys Val Arg Glu Gln Leu 
        115                 120                 125             


Cys Lys Leu Lys Gly Gly Val Val Val Asp Glu Leu Gly Cys Ser Arg 
    130                 135                 140                 


Gln Arg Ala Pro Ser Ser Lys Gln Val Asn Gly Val Gln Lys Gln Arg 
145                 150                 155                 160 


Arg Leu Ala Ala Asn Ala Arg Glu Arg Arg Arg Met His Gly Leu Asn 
                165                 170                 175     


His Ala Phe Asp Gln Leu Arg Asn Val Ile Pro Ser Phe Asn Asn Asp 
            180                 185                 190         


Lys Lys Leu Ser Lys Tyr Glu Thr Leu Gln Met Ala Gln Ile Tyr Ile 
        195                 200                 205             


Asn Ala Leu Ser Glu Leu Leu Gln Thr Pro Ser Gly Gly Glu Gln Pro 
    210                 215                 220                 


Pro Pro Pro Pro Ala Ser Cys Lys Ser Asp His His His Leu Arg Thr 
225                 230                 235                 240 


Ala Ala Ser Tyr Glu Gly Gly Ala Gly Asn Ala Thr Ala Ala Gly Ala 
                245                 250                 255     


Gln Gln Ala Ser Gly Gly Ser Gln Arg Pro Thr Pro Pro Gly Ser Cys 
            260                 265                 270         


Arg Thr Arg Phe Ser Ala Pro Ala Ser Ala Gly Gly Tyr Ser Val Gln 
        275                 280                 285             


Leu Asp Ala Leu His Phe Ser Thr Phe Glu Asp Ser Ala Leu Thr Ala 
    290                 295                 300                 


Met Met Ala Gln Lys Asn Leu Ser Pro Ser Leu Pro Gly Ser Ile Leu 
305                 310                 315                 320 


Gln Pro Val Gln Glu Glu Asn Ala Lys Thr Ser Pro Arg Ser His Arg 
                325                 330                 335     


Ser Asp Gly Glu Phe Ser Pro His Ser His Tyr Ser Asp Ser Asp Glu 
            340                 345                 350         


Ala Ser 
        


<210>  2
<211>  354
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  2

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


Gly Asp His His Arg Gln Pro Gln Pro His His Leu Pro Gln Pro Pro 
            20                  25                  30          


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


Tyr Pro Pro Glu Leu Ser Leu Leu Asp Ser Thr Asp Pro Arg Ala Trp 
    50                  55                  60                  


Leu Ala Pro Thr Leu Gln Gly Ile Cys Thr Ala Arg Ala Ala Gln Tyr 
65                  70                  75                  80  


Leu Leu His Ser Pro Glu Leu Gly Ala Ser Glu Ala Ala Ala Pro Arg 
                85                  90                  95      


Asp Glu Val Asp Gly Arg Gly Glu Leu Val Arg Arg Ser Ser Gly Gly 
            100                 105                 110         


Ala Ser Ser Ser Lys Ser Pro Gly Pro Val Lys Val Arg Glu Gln Leu 
        115                 120                 125             


Cys Lys Leu Lys Gly Gly Val Val Val Asp Glu Leu Gly Cys Ser Arg 
    130                 135                 140                 


Gln Arg Ala Pro Ser Ser Lys Gln Val Asn Gly Val Gln Lys Gln Arg 
145                 150                 155                 160 


Arg Leu Ala Ala Asn Ala Arg Glu Arg Arg Arg Met His Gly Leu Asn 
                165                 170                 175     


His Ala Phe Asp Gln Leu Arg Asn Val Ile Pro Ser Phe Asn Asn Asp 
            180                 185                 190         


Lys Lys Leu Ser Lys Tyr Glu Thr Leu Gln Met Ala Gln Ile Tyr Ile 
        195                 200                 205             


Asn Ala Leu Ser Glu Leu Leu Gln Thr Pro Ser Gly Gly Glu Gln Pro 
    210                 215                 220                 


Pro Pro Pro Pro Ala Ser Cys Lys Ser Asp His His His Leu Arg Thr 
225                 230                 235                 240 


Ala Ala Ser Tyr Glu Gly Gly Ala Gly Asn Ala Thr Ala Ala Gly Ala 
                245                 250                 255     


Gln Gln Ala Ser Gly Gly Ser Gln Arg Pro Thr Pro Pro Gly Ser Cys 
            260                 265                 270         


Arg Thr Arg Phe Ser Ala Pro Ala Ser Ala Gly Gly Tyr Ser Val Gln 
        275                 280                 285             


Leu Asp Ala Leu His Phe Ser Thr Phe Glu Asp Ser Ala Leu Thr Ala 
    290                 295                 300                 


Met Met Ala Gln Lys Asn Leu Ser Pro Ser Leu Pro Gly Ser Ile Leu 
305                 310                 315                 320 


Gln Pro Val Gln Glu Glu Asn Ser Lys Thr Ala Pro Arg Ser His Arg 
                325                 330                 335     


Ser Asp Gly Glu Phe Ser Pro His Ser His Tyr Ser Asp Ser Asp Glu 
            340                 345                 350         


Ala Ser 
        


<210>  3
<211>  354
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  3

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


Gly Asp His His Arg Gln Pro Gln Pro His His Leu Pro Gln Pro Pro 
            20                  25                  30          


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


Tyr Pro Pro Glu Leu Ser Leu Leu Asp Ser Thr Asp Pro Arg Ala Trp 
    50                  55                  60                  


Leu Ala Pro Thr Leu Gln Gly Ile Cys Thr Ala Arg Ala Ala Gln Tyr 
65                  70                  75                  80  


Leu Leu His Ser Pro Glu Leu Gly Ala Ser Glu Ala Ala Ala Pro Arg 
                85                  90                  95      


Asp Glu Val Asp Gly Arg Gly Glu Leu Val Arg Arg Ser Ser Gly Gly 
            100                 105                 110         


Ala Ser Ser Ser Lys Ser Pro Gly Pro Val Lys Val Arg Glu Gln Leu 
        115                 120                 125             


Cys Lys Leu Lys Gly Gly Val Val Val Asp Glu Leu Gly Cys Ser Arg 
    130                 135                 140                 


Gln Arg Ala Pro Ser Ser Lys Gln Val Asn Gly Val Gln Lys Gln Arg 
145                 150                 155                 160 


Arg Leu Ala Ala Asn Ala Arg Glu Arg Arg Arg Met His Gly Leu Asn 
                165                 170                 175     


His Ala Phe Asp Gln Leu Arg Asn Val Ile Pro Ser Phe Asn Asn Asp 
            180                 185                 190         


Lys Lys Leu Ser Lys Tyr Glu Thr Leu Gln Met Ala Gln Ile Tyr Ile 
        195                 200                 205             


Asn Ala Leu Ser Glu Leu Leu Gln Thr Pro Ser Gly Gly Glu Gln Pro 
    210                 215                 220                 


Pro Pro Pro Pro Ala Ser Cys Lys Ser Asp His His His Leu Arg Thr 
225                 230                 235                 240 


Ala Ala Ser Tyr Glu Gly Gly Ala Gly Asn Ala Thr Ala Ala Gly Ala 
                245                 250                 255     


Gln Gln Ala Ser Gly Gly Ser Gln Arg Pro Thr Pro Pro Gly Ser Cys 
            260                 265                 270         


Arg Thr Arg Phe Ser Ala Pro Ala Ser Ala Gly Gly Tyr Ser Val Gln 
        275                 280                 285             


Leu Asp Ala Leu His Phe Ser Thr Phe Glu Asp Ser Ala Leu Thr Ala 
    290                 295                 300                 


Met Met Ala Gln Lys Asn Leu Ser Pro Ser Leu Pro Gly Ser Ile Leu 
305                 310                 315                 320 


Gln Pro Val Gln Glu Glu Asn Ser Lys Thr Ser Pro Arg Ala His Arg 
                325                 330                 335     


Ser Asp Gly Glu Phe Ser Pro His Ser His Tyr Ser Asp Ser Asp Glu 
            340                 345                 350         


Ala Ser 
        


<210>  4
<211>  354
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  4

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


Gly Asp His His Arg Gln Pro Gln Pro His His Leu Pro Gln Pro Pro 
            20                  25                  30          


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


Tyr Pro Pro Glu Leu Ser Leu Leu Asp Ser Thr Asp Pro Arg Ala Trp 
    50                  55                  60                  


Leu Ala Pro Thr Leu Gln Gly Ile Cys Thr Ala Arg Ala Ala Gln Tyr 
65                  70                  75                  80  


Leu Leu His Ser Pro Glu Leu Gly Ala Ser Glu Ala Ala Ala Pro Arg 
                85                  90                  95      


Asp Glu Val Asp Gly Arg Gly Glu Leu Val Arg Arg Ser Ser Gly Gly 
            100                 105                 110         


Ala Ser Ser Ser Lys Ser Pro Gly Pro Val Lys Val Arg Glu Gln Leu 
        115                 120                 125             


Cys Lys Leu Lys Gly Gly Val Val Val Asp Glu Leu Gly Cys Ser Arg 
    130                 135                 140                 


Gln Arg Ala Pro Ser Ser Lys Gln Val Asn Gly Val Gln Lys Gln Arg 
145                 150                 155                 160 


Arg Leu Ala Ala Asn Ala Arg Glu Arg Arg Arg Met His Gly Leu Asn 
                165                 170                 175     


His Ala Phe Asp Gln Leu Arg Asn Val Ile Pro Ser Phe Asn Asn Asp 
            180                 185                 190         


Lys Lys Leu Ser Lys Tyr Glu Thr Leu Gln Met Ala Gln Ile Tyr Ile 
        195                 200                 205             


Asn Ala Leu Ser Glu Leu Leu Gln Thr Pro Ser Gly Gly Glu Gln Pro 
    210                 215                 220                 


Pro Pro Pro Pro Ala Ser Cys Lys Ser Asp His His His Leu Arg Thr 
225                 230                 235                 240 


Ala Ala Ser Tyr Glu Gly Gly Ala Gly Asn Ala Thr Ala Ala Gly Ala 
                245                 250                 255     


Gln Gln Ala Ser Gly Gly Ser Gln Arg Pro Thr Pro Pro Gly Ser Cys 
            260                 265                 270         


Arg Thr Arg Phe Ser Ala Pro Ala Ser Ala Gly Gly Tyr Ser Val Gln 
        275                 280                 285             


Leu Asp Ala Leu His Phe Ser Thr Phe Glu Asp Ser Ala Leu Thr Ala 
    290                 295                 300                 


Met Met Ala Gln Lys Asn Leu Ser Pro Ser Leu Pro Gly Ser Ile Leu 
305                 310                 315                 320 


Gln Pro Val Gln Glu Glu Asn Ala Lys Thr Ala Pro Arg Ser His Arg 
                325                 330                 335     


Ser Asp Gly Glu Phe Ser Pro His Ser His Tyr Ser Asp Ser Asp Glu 
            340                 345                 350         


Ala Ser 
        


<210>  5
<211>  354
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  5

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


Gly Asp His His Arg Gln Pro Gln Pro His His Leu Pro Gln Pro Pro 
            20                  25                  30          


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


Tyr Pro Pro Glu Leu Ser Leu Leu Asp Ser Thr Asp Pro Arg Ala Trp 
    50                  55                  60                  


Leu Ala Pro Thr Leu Gln Gly Ile Cys Thr Ala Arg Ala Ala Gln Tyr 
65                  70                  75                  80  


Leu Leu His Ser Pro Glu Leu Gly Ala Ser Glu Ala Ala Ala Pro Arg 
                85                  90                  95      


Asp Glu Val Asp Gly Arg Gly Glu Leu Val Arg Arg Ser Ser Gly Gly 
            100                 105                 110         


Ala Ser Ser Ser Lys Ser Pro Gly Pro Val Lys Val Arg Glu Gln Leu 
        115                 120                 125             


Cys Lys Leu Lys Gly Gly Val Val Val Asp Glu Leu Gly Cys Ser Arg 
    130                 135                 140                 


Gln Arg Ala Pro Ser Ser Lys Gln Val Asn Gly Val Gln Lys Gln Arg 
145                 150                 155                 160 


Arg Leu Ala Ala Asn Ala Arg Glu Arg Arg Arg Met His Gly Leu Asn 
                165                 170                 175     


His Ala Phe Asp Gln Leu Arg Asn Val Ile Pro Ser Phe Asn Asn Asp 
            180                 185                 190         


Lys Lys Leu Ser Lys Tyr Glu Thr Leu Gln Met Ala Gln Ile Tyr Ile 
        195                 200                 205             


Asn Ala Leu Ser Glu Leu Leu Gln Thr Pro Ser Gly Gly Glu Gln Pro 
    210                 215                 220                 


Pro Pro Pro Pro Ala Ser Cys Lys Ser Asp His His His Leu Arg Thr 
225                 230                 235                 240 


Ala Ala Ser Tyr Glu Gly Gly Ala Gly Asn Ala Thr Ala Ala Gly Ala 
                245                 250                 255     


Gln Gln Ala Ser Gly Gly Ser Gln Arg Pro Thr Pro Pro Gly Ser Cys 
            260                 265                 270         


Arg Thr Arg Phe Ser Ala Pro Ala Ser Ala Gly Gly Tyr Ser Val Gln 
        275                 280                 285             


Leu Asp Ala Leu His Phe Ser Thr Phe Glu Asp Ser Ala Leu Thr Ala 
    290                 295                 300                 


Met Met Ala Gln Lys Asn Leu Ser Pro Ser Leu Pro Gly Ser Ile Leu 
305                 310                 315                 320 


Gln Pro Val Gln Glu Glu Asn Ala Lys Thr Ser Pro Arg Ala His Arg 
                325                 330                 335     


Ser Asp Gly Glu Phe Ser Pro His Ser His Tyr Ser Asp Ser Asp Glu 
            340                 345                 350         


Ala Ser 
        


<210>  6
<211>  354
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  6

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


Gly Asp His His Arg Gln Pro Gln Pro His His Leu Pro Gln Pro Pro 
            20                  25                  30          


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


Tyr Pro Pro Glu Leu Ser Leu Leu Asp Ser Thr Asp Pro Arg Ala Trp 
    50                  55                  60                  


Leu Ala Pro Thr Leu Gln Gly Ile Cys Thr Ala Arg Ala Ala Gln Tyr 
65                  70                  75                  80  


Leu Leu His Ser Pro Glu Leu Gly Ala Ser Glu Ala Ala Ala Pro Arg 
                85                  90                  95      


Asp Glu Val Asp Gly Arg Gly Glu Leu Val Arg Arg Ser Ser Gly Gly 
            100                 105                 110         


Ala Ser Ser Ser Lys Ser Pro Gly Pro Val Lys Val Arg Glu Gln Leu 
        115                 120                 125             


Cys Lys Leu Lys Gly Gly Val Val Val Asp Glu Leu Gly Cys Ser Arg 
    130                 135                 140                 


Gln Arg Ala Pro Ser Ser Lys Gln Val Asn Gly Val Gln Lys Gln Arg 
145                 150                 155                 160 


Arg Leu Ala Ala Asn Ala Arg Glu Arg Arg Arg Met His Gly Leu Asn 
                165                 170                 175     


His Ala Phe Asp Gln Leu Arg Asn Val Ile Pro Ser Phe Asn Asn Asp 
            180                 185                 190         


Lys Lys Leu Ser Lys Tyr Glu Thr Leu Gln Met Ala Gln Ile Tyr Ile 
        195                 200                 205             


Asn Ala Leu Ser Glu Leu Leu Gln Thr Pro Ser Gly Gly Glu Gln Pro 
    210                 215                 220                 


Pro Pro Pro Pro Ala Ser Cys Lys Ser Asp His His His Leu Arg Thr 
225                 230                 235                 240 


Ala Ala Ser Tyr Glu Gly Gly Ala Gly Asn Ala Thr Ala Ala Gly Ala 
                245                 250                 255     


Gln Gln Ala Ser Gly Gly Ser Gln Arg Pro Thr Pro Pro Gly Ser Cys 
            260                 265                 270         


Arg Thr Arg Phe Ser Ala Pro Ala Ser Ala Gly Gly Tyr Ser Val Gln 
        275                 280                 285             


Leu Asp Ala Leu His Phe Ser Thr Phe Glu Asp Ser Ala Leu Thr Ala 
    290                 295                 300                 


Met Met Ala Gln Lys Asn Leu Ser Pro Ser Leu Pro Gly Ser Ile Leu 
305                 310                 315                 320 


Gln Pro Val Gln Glu Glu Asn Ser Lys Thr Ala Pro Arg Ala His Arg 
                325                 330                 335     


Ser Asp Gly Glu Phe Ser Pro His Ser His Tyr Ser Asp Ser Asp Glu 
            340                 345                 350         


Ala Ser 
        


<210>  7
<211>  354
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  7

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


Gly Asp His His Arg Gln Pro Gln Pro His His Leu Pro Gln Pro Pro 
            20                  25                  30          


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


Tyr Pro Pro Glu Leu Ser Leu Leu Asp Ser Thr Asp Pro Arg Ala Trp 
    50                  55                  60                  


Leu Ala Pro Thr Leu Gln Gly Ile Cys Thr Ala Arg Ala Ala Gln Tyr 
65                  70                  75                  80  


Leu Leu His Ser Pro Glu Leu Gly Ala Ser Glu Ala Ala Ala Pro Arg 
                85                  90                  95      


Asp Glu Val Asp Gly Arg Gly Glu Leu Val Arg Arg Ser Ser Gly Gly 
            100                 105                 110         


Ala Ser Ser Ser Lys Ser Pro Gly Pro Val Lys Val Arg Glu Gln Leu 
        115                 120                 125             


Cys Lys Leu Lys Gly Gly Val Val Val Asp Glu Leu Gly Cys Ser Arg 
    130                 135                 140                 


Gln Arg Ala Pro Ser Ser Lys Gln Val Asn Gly Val Gln Lys Gln Arg 
145                 150                 155                 160 


Arg Leu Ala Ala Asn Ala Arg Glu Arg Arg Arg Met His Gly Leu Asn 
                165                 170                 175     


His Ala Phe Asp Gln Leu Arg Asn Val Ile Pro Ser Phe Asn Asn Asp 
            180                 185                 190         


Lys Lys Leu Ser Lys Tyr Glu Thr Leu Gln Met Ala Gln Ile Tyr Ile 
        195                 200                 205             


Asn Ala Leu Ser Glu Leu Leu Gln Thr Pro Ser Gly Gly Glu Gln Pro 
    210                 215                 220                 


Pro Pro Pro Pro Ala Ser Cys Lys Ser Asp His His His Leu Arg Thr 
225                 230                 235                 240 


Ala Ala Ser Tyr Glu Gly Gly Ala Gly Asn Ala Thr Ala Ala Gly Ala 
                245                 250                 255     


Gln Gln Ala Ser Gly Gly Ser Gln Arg Pro Thr Pro Pro Gly Ser Cys 
            260                 265                 270         


Arg Thr Arg Phe Ser Ala Pro Ala Ser Ala Gly Gly Tyr Ser Val Gln 
        275                 280                 285             


Leu Asp Ala Leu His Phe Ser Thr Phe Glu Asp Ser Ala Leu Thr Ala 
    290                 295                 300                 


Met Met Ala Gln Lys Asn Leu Ser Pro Ser Leu Pro Gly Ser Ile Leu 
305                 310                 315                 320 


Gln Pro Val Gln Glu Glu Asn Ala Lys Thr Ala Pro Arg Ala His Arg 
                325                 330                 335     


Ser Asp Gly Glu Phe Ser Pro His Ser His Tyr Ser Asp Ser Asp Glu 
            340                 345                 350         


Ala Ser 
        


