Incidence, timing, and clinical significance of adverse immune events after gene replacement therapy: A systematic review and meta-analysis

Molecular Therapy 2026 Open access

Read full text
Authors: Niccolo Maurizi, Enrico Ammirati, Elizabeth Silver, Kimberly Hong, Quan M. Bui, Alessia Argirò, Iacopo Olivotto, Eric D. Adler
DOI: 10.1016/j.ymthe.2026.01.004
Cited by: 11
References: 97

Abstract

vg/kg significantly increased AE risk (OR = 5.59 [1.35-12.2], p = 0.018; OR = 2.31 [1.04-5.53], p = 0.041), whereas combined corticosteroid, anti-CD20, mTOR- and calcineurin inhibitor regimens were protective (OR = 0.67 [0.47-0.96], p = 0.040). At least five cases of TMA, one of myocarditis, and three deaths could not be included in the present analysis because these events were described in company statements. These findings underscore that one-third of AAV recipients experience immunotoxicity, predominantly early and mild, and support proactive immunosuppression and vector optimization to enhance safety.

Fields of Study & Subjects

Virus-based gene therapy research CRISPR and Genetic Engineering Viral gastroenteritis research and epidemiology

Publication details

Journal / source
Molecular Therapy
Publisher
Elsevier BV
Volume
34
Issue
3
Pages
1340–1351
Publication date
10 January 2026
Language
EN