ArticlePharmaceutical research2026
Critical evaluation of the impact of ssDNA cargo length on AAV stability - a case study.
Article in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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11 authors.
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Abstract
purposeTo evaluate how ssDNA cargo size influences the physicochemical characteristics and stability behavior of AAVX vectors under thermal, chemical, and other accelerated stress conditions.
methodsAAVX vectors with differing ssDNA cargo length (i.e. 2.8 kb and 4.6 kb) were analyzed under manufacturing-relevant, storage-related, and accelerated stress conditions using complementary analytical methods to assess capsid stability, genome integrity, potency, and capsid chemical modifications.
resultsThermal and chemical denaturation experiments showed similar capsid unfolding across the cargo sizes tested. Under accelerated thermal stress (40°C), the shorter-genome vector showed less ssDNA release and better preservation of capsid and genome titers than the longer-genome vector. Fragmentation of encapsulated ssDNA was also observed for the shorter cargo. Capsid chemical modifications, including asparagine deamidation and aspartic acid isomerization, increased markedly at 40°C.
conclusionsThese findings provide a case-study view of how cargo size can affect AAV stability readouts in a condition-dependent behavior and highlight the value of multi-attribute characterization for evaluating AAV vector stability. In addition, our results also suggest that suggest that, under the conditions tested for AAVX, the same capsid may be useful for evaluating vector stability with different genome sizes.
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