Helper system for the increase in activity of the aav vector production -

摘要

Novel nucleic acid molecules are provided having adeno-associated virus (AAV) coding regions that are capable of expressing necessary AAV functions to complement an AAV vector in the production of recombinant AAV (rAAV) virions. The molecules feature a nucleotide sequence that is substantially homologous to an AAV p5 promoter region, wherein the p5 promoter region is situated in the molecules in a site that is other than its natural position relative to the AAV rep coding region in the wild-type AAV genome. AAV helper function constructs are also provided, comprising the instant nucleic acid molecules embodied in a replicon that is capable of being transcribed and translated to express complementing AAV helper functions in a suitable host cell. Novel AAV packaging cells and AAV producer cells are provided, which contain the AAV helper constructs of the invention, and methods of producing enhanced levels of rAAV virions using the AAV helper constructs of the invention are also provided. Methods are also provided for producing rAAV virions without the concomitant production of significant levels of wild-type AAV.