Abstract: Provided herein are methods of transducing a recombinant viral, e.g., retroviral, vector, improving the transgene expression from a recombinant viral vector, and reducing titers of neutralizing antibodies that bind a recombinant viral vector. In general, these methods include administering to a subject a recombinant viral vector and an effective amount of an immunosuppressive regimen.

Abstract: Provided herein are polynucleotides, rAAV vectors, pharmaceutical compositions, and methods of making and using the same, e.g., for treatment of cystic fibrosis (CF). For example, the disclosure provides a recombinant adeno-associated vims (rAAV) that includes, in one embodiment, an AV.TL65 capsid protein and a polynucleotide that includes an F5 enhancer and a tg83 promoter operably linked to a CFTR?R minigene, pharmaceutical compositions thereof, and methods of use thereof, e.g., for treatment of CF.

Abstract: The disclosure provides methods of expressing a transgene in a cell, methods of treating disorders in a subject in need thereof, and pharmaceutical compositions. In particular, the methods involve contacting a cell (e.g., a cell of a subject suffering from a disorder such as cystic fibrosis) with a recombinant adeno-associated virus (rAAV) that includes, in one embodiment, an AV.TL65 capsid protein and a polynucleotide that includes a transgene in combination with an augmenter of AAV transduction, thereby expressing the transgene in the cell. The disclosure also provides pharmaceutical compositions that include an rAAV that includes, in one embodiment, an AV.TL65 capsid protein and a polynucleotide including a transgene in combination with one or more augmenters.