Recombinant aavs having useful transcytosis properties

Abstract

The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associate viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

1 .- 3 . (canceled) 
     
     
         4 . A host cell containing a nucleic acid that comprises a coding sequence selected from the group consisting of: SEQ ID NOs: 10-14 that is operably linked to a promoter. 
     
     
         5 . A composition comprising the host cell of  claim 4  and a sterile cell culture medium. 
     
     
         6 . A composition comprising the host cell of  claim 5  and a cryopreservative. 
     
     
         7 .- 38 . (canceled) 
     
     
         39 . A recombinant AAV (rAAV) comprising an AAV capsid protein having an amino acid sequence of SEQ ID NO: 1 with one or more amino acid mutations selected from the group consisting of Y445H, H527Y, I647T, and R533S. 
     
     
         40 . The rAAV of  claim 39  further comprising at least one transgene. 
     
     
         41 . A method for delivering a transgene to a subject comprising administering the rAAV of  claim 40  to a subject, wherein the rAAV infects cells of a muscle tissue of the subject. 
     
     
         42 . The method of  claim 41 , wherein the at least one transgene encodes a protein or a small interfering nucleic acid. 
     
     
         43 . The method of claim of  claim 41 , wherein the muscle tissue is skeletal muscle or heart tissue. 
     
     
         44 . The method of  claim 41 , wherein the rAAV is administered intravenously, intravascularly, or intramuscularly. 
     
     
         45 . The rAAV of  claim 39 , wherein the one or more amino acid mutations are H527Y and R533S. 
     
     
         46 . The rAAV of  claim 45  further comprising at least one transgene. 
     
     
         47 . A method for delivering a transgene to a subject comprising administering the rAAV of  claim 46  to a subject, wherein the rAAV infects cells of a muscle tissue of the subject. 
     
     
         48 . The method of  claim 47 , wherein the at least one transgene encodes a protein or a small interfering nucleic acid. 
     
     
         49 . The method of claim of  claim 47 , wherein the muscle tissue is skeletal muscle or heart tissue. 
     
     
         50 . The method of  claim 47 , wherein the rAAV is administered intravenously, intravascularly, or intramuscularly. 
     
     
         51 . A nucleic acid encoding the rAAV of  claim 39 . 
     
     
         52 . A nucleic acid encoding the rAAV of  claim 45 . 
     
     
         53 . A recombinant AAV (rAAV) comprising an AAV capsid protein having one or more amino acid mutations at positions corresponding to Y445H, H527Y, I647T, and R533S of SEQ ID NO: 1. 
     
     
         54 . The rAAV of  claim 54 , wherein the AAV capsid protein has amino acid mutations at positions corresponding to H527Y and R533S of SEQ ID NO: 1. 
     
     
         55 . A method for delivering a transgene to a subject comprising administering the rAAV of  claim 54  to a subject, wherein the rAAV further comprises the transgene, and wherein the rAAV infects cells of a muscle tissue of the subject.