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.

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.

Gene therapy

Cardiomyopathies

Myocarditis

Adeno-associated virus

pathogen-associated molecular patterns

nuclear factor kappa b

interferon-regulatory factor)

melanoma differentiation-associated protein 5

antigen presenting cell

thrombotic microangiopathy

aspartate transaminase

spinal muscular atrophy

X-linked myotubular myopathy

Food and Drug Administration

Enzyme-Linked ImmunoSpot

Duchenne's muscular dystrophy

magnetic resonance imaging

tumor necrosis factor-alpha receptor II IgG-Fc fusion protein

human acid-alpha glucosidase

insulin-like growth factor 2 variant

major histocompatibility complex

acute respiratory distress syndrome

left ventricular ejection fraction

extracorporeal membrane oxygenation

bilevel positive airway pressure

brain natriuretic peptide

intravenous immunoglobulin

© 2023 The Author(s). Published by Elsevier B.V.