Recombinant AAV vectors useful for reducing immunity against transgene products

A method of delivering a transgene to target cells of a subject, the method comprising intramuscularly administering to the subject a recombinant Adeno-Associated Virus (rAAV) comprising the transgene,

• wherein the transgene comprises a promoter operably linked to a nucleic acid sequence that encodes an RNA transcript that comprises two different immune-associated miRNA binding sites, wherein the two different immune-associated miRNA binding sites comprise an miRNA pair selected from:
• (i) miR-142-3p and miR-155, (ii) miR-146a and miR-150, (iii) miR-424 and miR-150, (iv) miR-181a and miR-21, (v) miR-16-1 and miR-150, (vi) miR-146 and miR-181a, (vii) miR-31 and miR-181a, (viii) miR-146a and miR-16-1, (ix) miR-150 and miR-181a, (x) miR-16-1 and miR-181a, and (xi) miR-142-3p and miR-223;
• wherein the rAAV infects the target cells of the subject,
• wherein the target cells are muscle cells, and
• wherein, following the administration, the transgene is expressed in the muscle cells at a higher level than in antigen presenting cells of the subject.