Methods for increasing the production of high titre stocks of recombinant adeno-associated virus (AAV)

摘要

Methods and compositions for increasing the production of high titre stocks of recombinant adeno-associated AAV (rAAV) through regulation of expression of the AAV REP and CAP proteins are described. The methods and compositions are based on the observation that the low level expression of the AAV REP protein increases the production of AAV viral capsid protein and efficiency of packaging resulting in production of higher titre recombinant viral stocks. Also described are rAAV vectors that direct the expression of AAV REP and CAP proteins and the use of such vectors for the production of stable cell lines capable of generating high titre rAAV vectors. Methods for regulating the expression of the AAV REP gene at the transcriptional and post-translational level are also provided.