Why the study?
Pre-existing immunity, high seroprevalence, and broad antigenic cross-reactivity of primate-derived AAVs limit patient eligibility and preclude therapeutic redosing in gene therapy.
Does AAV.div3A enable gene therapy redosing by evading neutralizing antibodies in preclinical models?
Population
Mice, including a Pompe disease model
Comparison
AAV.div3A or AAV.div3A-M1 vs pre-existing or vector-induced immunity
Design
Preclinical experimental study
Key result
Engineered non-mammalian AAV capsids (AAV.div3A and div3A-M1) fully evaded neutralization and significantly increased therapeutic GAA levels upon redosing in a Pompe disease model.
Authors
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Enables AAV redosing in Pompe models; leaves open human translation and safety trials.
Does AAV.div3A enable gene therapy redosing by evading neutralizing antibodies in preclinical models?
Engineered non-mammalian AAV capsids completely evade pre-existing neutralizing antibodies, enabling effective gene therapy redosing in preclinical models.
Loeb et al. (2025) studied Pompe disease. AAV.div3A and div3A-M1 was evaluated on Therapeutic GAA levels. Engineered non-mammalian AAV capsids (AAV.div3A and div3A-M1) fully evaded neutralization and significantly increased therapeutic GAA levels upon redosing in a Pompe disease model.