FIG. 4.

Schematic diagram illustrating the downstream process described in the text. The entire culture volume is processed first by mechanical homogenization (1) and then returned to the stirred-tank bioreactor for nuclease treatment (2). Microfiltration (3) removes particulates and clarifies the supernatant. Immunoaffinity chromatography (4) is used for rAAV particle recovery and purification. Gel-exclusion chromatography (5) provides polishing and buffer exchange. Tangential flow filtration (TFF) is performed to concentrate the vector and diafiltrate into the final formulation buffer (6). Finally, the concentrated vector is sterilized by filtration and filled into vials (7).