Compositions and methods for increasing or enhancing transduction of gene therapy vectors and for removing or reducing immunoglobulins

A method of treating a disease with a recombinant adeno-associated virus (AAV) vector in a human in need thereof, comprising:

• step (a):
• administering to said human an effective amount of a cysteine protease immunoglobulin G-degrading enzyme polypeptide comprising a sequence at least 90% identical to the sequence of any of SEQ ID NO:3-43 or 48;
• followed by
• step (b):
• within about 72 hours of step (a), administering to said human a recombinant AAV vector comprising a heterologous polynucleotide encoding a polypeptide or an inhibitory nucleic acid;
• wherein said cysteine protease immunoglobulin G-degrading enzyme polypeptide is effective to degrade or digest neutralizing anti-AAV antibodies.

A method of increasing cell transduction efficiency of a recombinant adeno-associated virus (AAV) vector in a human in need thereof, comprising:

• (a) administering to said human an effective amount of an immunoglobulin G-degrading enzyme polypeptide, wherein said immunoglobulin G-degrading enzyme polypeptide is a cysteine protease effective to degrade or digest neutralizing anti-AAV antibodies in said human;
• and
• (b) administering to said human a recombinant AAV vector within about 72 hours after the immunoglobulin G-degrading enzyme polypeptide is administered,
• wherein said immunoglobulin G-degrading enzyme polypeptide is effective to degrade or digest neutralizing anti-AAV antibodies that inhibit cell transduction of said recombinant AAV vector in said human, and wherein cell transduction efficiency of said recombinant AAV is increased.