Does exo-AAV8 improve liver gene transfer and evade preexisting neutralizing antibodies compared to standard AAV8 in mouse models and human sera?
Exosome-enveloped AAV vectors enhance liver gene transfer and evade preexisting neutralizing antibodies, potentially improving the safety and efficacy of gene therapy.
vector genomes per kilogram of exo-AAV8 vectors, a staggering ∼1 log increase in hF.IX transgene expression was observed, leading to superior correction of clotting time. Enhanced liver expression was also associated with an increase in the frequency of regulatory T cells in lymph nodes. The efficiency of exo- and standard AAV8 vectors in evading preexisting NAbs to the capsid was then evaluated in a passive immunization mouse model and in human sera. Exo-AAV8 gene delivery allowed for efficient transduction even in the presence of moderate NAb titers, thus potentially extending the proportion of subjects eligible for liver gene transfer. Exo-AAV vectors therefore represent a platform to improve the safety and efficacy of liver-directed gene transfer.
Meliani et al. (Mon,) studied this question.
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