Gene therapy vector-related myocarditis

• Published in: International journal of cardiology Vol. 398; p. 131617
• Main Authors: Silver, Elizabeth, Argiro, Alessia, Hong, Kimberly, Adler, Eric
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2024
• Subjects: Cardiomyopathies; Dependovirus - genetics; Gene therapy; Genetic Therapy - methods; Genetic Vectors; Humans; Myocarditis; Myocarditis - genetics; Myocarditis - therapy; FDA; MRI; BNP; LVEF; ALT; MHC; MDA5; hGAA; Cardiomyopathies; DMD; TLR; WT; ARDS; ECMO; vIGF2; AST; SMA; NF-kb; TMA; XLMTM; IVIG; BiPAP; ELISPOT; Nab; Myocarditis; PAMP; APC; AAV; Gene therapy; IRF; TNFRII-Fc
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2023.131617

Gene therapy is a technique to correct genetic abnormalities, through introduction of a functional gene or through direct genome editing. Adeno-associated virus (AAV)-mediated gene replacement shows promise for targeted therapies in treatment of inherited cardiomyopathies and is the most used approach in clinical trials. However, immune responses from the host to the virus and gene product pose delivery and safety challenges. This review explores the immunological reactions to AAV-based gene therapy, their potential toxic effects, with a focus on myocarditis, and future directions for gene therapy. Central Illustration: Mechanisms of gene therapy toxicity. TLR: toll-like receptor. PAMP: pathogen-associated molecular patterns, APC: antigen-presenting cell, NF-kB: nuclear factor kappa B, ITR: inverted terminal repeats, pA: poly-A tail. Created with BioRender.com [Display omitted] •AAV-delivered gene therapy has shown promising results in clinical trials for inherited diseases.•Immune reactions may develop against the transgene or vector, leading to possible adverse events.•Standardized immunosuppressive regimens may be important for increasing gene therapy safety.