The Problem of Partials: Redefining The Analytical Frameworks Surrounding Capsid Characterization

By Achille François, Viralgen

For years, empty and partially packaged capsids were not treated as serious impurities, partly because analytical tools could not reliably detect them, and potency was assumed to track closely with vector genome titer. That assumption has since been overturned. Modern high-resolution methods have revealed that many AAV preparations contain substantial proportions of partially packaged capsids, which arise throughout production and are significantly harder to remove than empties due to their similar charge and density properties to full capsids.

These partial particles can compete with fully packaged genomes during intracellular processing, reducing potency and introducing uncertainty in transgene biodistribution. Early findings suggesting that complementary partials could recombine into functional genomes delayed their recognition as impurities, but such events are too inconsistent to be clinically relied upon. Regulators now expect clear characterization and control strategies for each capsid subspecies, making analytical distinction between empty, partial, and full particles a core requirement for next-generation AAV programs.