GENERATION OF HIGH TITERS OF RECOMBINANT AAV VECTORS

摘要

AAV vectors may have utility for gene therapy but heretofore a significant obstacle has been the inability to generate sufficient quantities of such recombinant vectors in amounts that would be clinically useful for human gene therapy application. Stable, helper-free AAV packaging cell lines have been elusive, mainly due to the activities of Rep protein, which down-regulates its own expression and reverses cellular immortalization. This invention provides packaging systems and processes for packaging AAV vectors that effectively circumvent these problems by replacing the AAV p5 promoter with a heterologous promoter (as depicted in the figure) and that allow for substantially increased packaging efficiency.