Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
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.

PubMed Disclaimer

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.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Duan D. Systemic delivery of adeno-associated viral vectors. Curr. Opin. Virol. 2016;21:16–25. doi: 10.1016/j.coviro.2016.07.006. - DOI - PMC - PubMed
    1. Toro W., Yang M., Georgieva M., Anderson A., LaMarca N., Patel A., Akbarnejad H., Dabbous O. Patient and Caregiver Outcomes After Onasemnogene Abeparvovec Treatment: Findings from the Cure SMA 2021 Membership Survey. Adv. Ther. 2023 doi: 10.1007/s12325-023-02685-w. - DOI - PMC - PubMed
    1. Mullard A. FDA approves first gene therapy for Duchenne muscular dystrophy, despite internal objections. Nat. Rev. Drug Discov. 2023;22:610. doi: 10.1038/d41573-023-00103-y. - DOI - PubMed
    1. Shieh P.B., Bönnemann C.G., Müller-Felber W., Blaschek A., Dowling J.J., Kuntz N.L., Seferian A.M. Re: "Moving Forward After Two Deaths in a Gene Therapy Trial of Myotubular Myopathy" by Wilson and Flotte. Hum. Gene Ther. 2020;31:787. doi: 10.1089/hum.2020.217. - DOI - PMC - PubMed
    1. Philippidis A. Fourth Boy Dies in Clinical Trial of Astellas' AT132. Hum. Gene Ther. 2021;32:1008–1010. doi: 10.1089/hum.2021.29182.bfs. - DOI - PubMed

Publication types

LinkOut - more resources