PH-dependent DNA degradation pathways for adeno-associated virus gene therapy.

ABSTRACT: Adeno-associated virus (AAV) vector genome degradation mechanisms that reduce transduction efficiency and viral potency must be understood to define critical quality attributes to ensure safety and efficacy. Here, we report that under prolonged storage at 25°C with two capsid types from clade C and E and varying buffer conditions the observation of degradation of rAAV DNA. Studies revealed two main degradation mechanisms: chemical degradation of encapsidated DNA at acidic pH and ejection of DNA at basic pH, with both occurring at neutral pH. Moreover, storage of clade E capsid in acidic pH at 25°C for 7 days showed >50% potency loss, which strongly correlated with a drop in encapsidated single-stranded DNA (ssDNA) (>40%) but not with conventional attributes used to characterize AAV stabili

SUBMITTER: Plegaria JS 

PROVIDER: S-EPMC12466224 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature