Cell culture methods involving HDAC inhibitors or rep proteins

A method of developing a stable cell line comprising a recombinant AAV (rAAV) vector sequence stably integrated into chromosome 19 for producing rAAV, the method comprising:

• a) providing a rAAV vector comprising the rAAV vector sequence and a rep mRNA selected from the group consisting of rep68 mRNA, rep78 mRNA, and a combination thereof to a HeLa cell culture;
• b) culturing the HeLa cell culture under conditions that allow for integration of the rAAV vector into the HeLa cell genome;
• c) identifying a HeLa cell that contains the rAAV vector sequence integrated into chromosome 19 of the HeLa cell genome;
• and
• d) culturing the mammalian cell under conditions that allow for generation of a cell line that produces rAAV,
• wherein the rAAV produced by the cell line is at a titer of at least 8.5×1010 GC/ml when the HeLa cell culture of d) is cultured for at least four days.