Adverse effects of intravenous LNP-mediated mRNA therapy in clinical trials: a systematic review and meta-analysis.

Abstract

Introduction: Intravenous LNP-mediated mRNA therapy holds promise for treating various diseases, yet its safety, particularly regarding adverse events, remains a critical concern. This review systematically evaluates the adverse effects associated with this therapeutic approach.

Methods: A comprehensive search of PubMed was conducted for clinical trials on intravenous LNP-mediated mRNA therapies. Data extraction focused on study design, participant demographics, and adverse events. Meta-analysis was performed to assess the incidence of treatment-emergent adverse events (TEAEs) and common manifestations. The risk of bias was assessed using the ROBINS-I tool.

Results: A total of six phase 1/2 clinical trials on intravenous LNP-mediated mRNA therapies were included, with sample sizes ranging from 6 to 38 participants. The pooled incidence of TEAEs was 92.2% (95% CI: 77.7%-99.4%). Sensitivity analysis indicated that excluding one study with a single smaller dose reduced heterogeneity to 6.8%. The incidence of severe TEAEs was 9.2% (95% CI: 0%-38.1%) and showed substantial heterogeneity (I² = 89.87%), which was likely influenced by factors such as higher doses, multiple administrations, and patient-specific conditions like comorbidities.

Conclusion: While low-dose, single-dose intravenous LNP-mediated mRNA therapies generally have a manageable safety profile, higher doses or repeated administrations may increase the risk of severe adverse events.

Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42025643741.