Novel recombinant adeno-associated virus capsids with enhanced human skeletal muscle tropism

Abstract

The present invention relates to variant AAV capsid polypeptides, wherein the variant AAV capsid polypeptides exhibit increased transduction and/or tropism in human muscle tissue or cells as compared non-variant parent capsid polypeptides.

1 .- 15 . (canceled) 
     
     
         16 . An adeno-associated virus (AAV) vector comprising a nucleic acid sequence encoding a variant AAV capsid polypeptide, wherein said variant AAV capsid polypeptide exhibits increased transduction or tropism in human muscle tissue or cells as compared to a non-variant parent capsid polypeptide. 
     
     
         17 . The AAV vector of  claim 16 , wherein said variant AAV capsid polypeptide exhibits increased transduction as compared to a non-variant parent capsid polypeptide. 
     
     
         18 . The AAV vector of  claim 16 , wherein said variant AAV capsid polypeptide exhibits increased tropism as compared to a non-variant parent capsid polypeptides. 
     
     
         19 . The AAV vector of  claim 16 , wherein said variant AAV capsid polypeptide further exhibits an enhanced neutralization profile as compared to a non-variant parent capsid polypeptide. 
     
     
         20 . The AAV vector of  claim 16 , wherein said variant AAV capsid polypeptide further exhibits increased transduction or tropism in one or more non-muscle human tissues as compared to non-variant parent capsid polypeptide. 
     
     
         21 . The AAV vector of  claim 16 , wherein said variant AAV capsid polypeptide exhibits increased transduction of human muscle tissue or cells in vivo as compared to a non-variant parent capsid polypeptide. 
     
     
         22 . The AAV vector of  claim 16 , wherein said variant AAV capsid polypeptide exhibits increased transduction of human muscle tissue or cells in vitro as compared to a non-variant parent capsid polypeptide. 
     
     
         23 . The AAV vector of  claim 16 , wherein said variant AAV capsid polypeptide exhibits increased transduction of a human muscle tissue explant ex vivo as compared to a non-variant parent capsid polypeptide. 
     
     
         24 . The AAV vector of  claim 16 , wherein said vector further comprises a nucleic acid sequence selected from the group consisting of a non-coding RNA, a coding sequence, an expression cassette, a multi-expression cassette, a sequence for homologous recombination, a genomic gene targeting cassette, and a therapeutic expression cassette. 
     
     
         25 . The AAV vector of  claim 24 , wherein said variant AAV capsid polypeptide allows for nucleic acid expression similarly to a non-variant parent capsid polypeptide. 
     
     
         26 . The AAV vector of  claim 24 , wherein said expression cassette is a CRISPR/CAS expression system. 
     
     
         27 . The AAV vector of  claim 24 , wherein said therapeutic expression cassette encodes a therapeutic protein or antibody. 
     
     
         28 . The AAV vector of  claim 16 , wherein said variant AAV capsid polypeptide sequence is selected from the group consisting of AAV-NP6 (SEQ ID NO: 1), AAV-NP20 (SEQ ID NO: 2), AAV-NP22, (SEQ ID NO: 3), AAV-NP36 (SEQ ID NO: 4), AAV-NP66 (SEQ ID NO: 5), AAV-NP81 (SEQ ID NO: 6), and AAV-NP94 (SEQ ID NO: 7). 
     
     
         29 .- 39 . (canceled)