Accelerated Yield Optimization Of Affinity Capture Of A Challenging AAV5 Serotype With 96-Well Chromatography Screening Plates

AAV5 continues to challenge downstream purification teams, often underperforming in affinity capture steps that work well for other serotypes. This work explores a rapid, high‑throughput approach to overcoming those limitations by systematically optimizing affinity elution conditions. Using 96‑well chromatography screening plates paired with mass photometry and ddPCR, the study evaluates how buffer chemistry, pH, and additives influence recovery and capsid quality. Simple acidic buffers emerged as a key driver of successful elution, dramatically improving yields while preserving compatibility with downstream polishing steps. The optimized conditions were then confirmed at column scale, demonstrating strong translation from screening to process‑relevant formats. For teams facing low recoveries or extended development timelines with AAV5, this strategy offers a practical path to faster, more controlled process optimization. Explore the full findings to see how high‑throughput screening can reshape AAV purification workflows.