AAV Forced Degradation Capabilities

Poster Authors:

Lucy Ballantine, Senior Technical Specialist; Rebecca Rich, Senior Scientist; Amy McGeoch, Industrial Placement Student

Pharmaron – Gene Therapy, Liverpool, UK

AAV Forced Degradation Study in AAV9

Pharmaron has applied AAV forced degradation studies across its AAV process platform for multiple serotypes. In this poster study, commercially available AAV9 was used to map real-world degradation pathways and confirm which analytical readouts are truly stability-indicating.

AAV9 was challenged with common stressors including pH stress, UV light, mechanical agitation, temperature holds (25°C and 50°C), and repeated freeze-thaw cycles then analyzed using an orthogonal panel of assays spanning identity, purity, potency, and higher-order structure. Results showed the highest degradation at 50°C with increased high molecular weight species and reduced full capsid content plus a drop in infectivity. UV exposure also drove VP3 oxidation and a measurable loss of potency. In contrast, low and high pH conditions produced comparatively low degradation, freeze-thaw showed modest aggregation trends at higher cycle counts, and agitation produced no measurable change across the methods used. Notably, capsid and genome titers remained largely unchanged across conditions, reinforcing why potency and structural assays are essential in an AAV forced degradation strategy.