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Review
. 2023 Nov 1;31(11):3123-3126.
doi: 10.1016/j.ymthe.2023.10.015. Epub 2023 Oct 10.

Lethal immunotoxicity in high-dose systemic AAV therapy

Dongsheng Duan  1
Affiliations
Review

Lethal immunotoxicity in high-dose systemic AAV therapy

Dongsheng Duan. Mol Ther. .

Abstract

High-dose systemic gene therapy with adeno-associated virus (AAV) is in clinical trials to treat various inherited diseases. Despite remarkable success in spinal muscular atrophy and promising results in other diseases, fatality has been observed due to liver, kidney, heart, or lung failure. Innate and adaptive immune responses to the vector play a critical role in the toxicity. Host factors also contribute to patient death. This mini-review summarizes clinical findings and calls for concerted efforts from all stakeholders to better understand the mechanisms underlying lethality in AAV gene therapy and to develop effective strategies to prevent/treat high-dose systemic AAV-gene-therapy-induced immunotoxicity.

Keywords: AAV; ARDS; CRISPR; DMD; Duchenne muscular dystrophy; acute respiratory distress syndrome; adeno-associated virus; death; immunotoxicity; innate immune response; systemic gene therapy.

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Conflict of interest statement

Declaration of interests D.D. is a member of the scientific advisory board for Solid Biosciences and an equity holder of Solid Biosciences, a member of the scientific advisory board for Sardocor Corp., and an inventor of several issued and filed patents on DMD gene therapy and AAV vectors.

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