ArticleFrontiers in pharmacology2025
Dihydroartemisinin decreases pre-existing neutralizing antibodies against adeno-associated virus in challenged mice.
Article in Frontiers in pharmacology, 2025. 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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Abstract
Introduction: The high prevalence of pre-existing neutralizing antibodies (NAbs) against adeno-associated virus (AAV) poses a major obstacle to in vivo gene therapy. Current immunosuppressive (IS) strategies, such as corticosteroids, are limited by toxicity and adverse effects. To explore safer alternatives, we evaluated dihydroartemisinin (DHA), a synthetic derivative of artemisinin inspired by traditional Chinese medicine (TCM), as a potential IS agent. Methods: In vivo experiments were conducted by administering DHA at either 30 or 210 days post-injection (PI) of rAAVDJ vectors. Anti-AAV NAb levels, transgene expression, and vector genome biodistribution were assessed. Flow cytometry was used to quantify CD20 Results: DHA administration significantly reduced anti-AAV NAb levels without compromising transgene expression or vector genome distribution. DHA treatment resulted in a reduction of splenic CD20 Discussion: These findings suggest that DHA is a safe and effective agent for modulating humoral immune responses to AAV vectors. Our results provide proof-of-concept evidence supporting the use of TCM-derived compounds to address immunological barriers in gene therapy.
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