Impact of Low pH Affinity Chromatography Elution on AAV Transduction

Affinity chromatography is an effective method for purifying AAV particles for gene therapy, but concerns exist regarding the impact of acidic pH elution on virus stability.

Key findings:

• AAV capsids showed no significant loss of stability or infectivity at 25°C for up to 4 hours, but AAV8 experienced aggregation and infectivity loss at 40°C.
• Virus aggregation observed during downstream purification was linked to capsid concentration rather than the specific capture process used.
• Immediate pH neutralization after acidic elution (as low as pH 2) helps mitigate risks of capsid inactivation and destabilization.