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

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: = 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.