Journal Article

Strategies to reduce the risks of mRNA drug and vaccine toxicity

Rogers, Maximillian A, Jacquinet, Eric, Amiji, Mansoor M, Bitounis, Dimitrios

2024

Overview

mRNA formulated with lipid nanoparticles is a transformative technology that has enabled the rapid development and administration of billions of coronavirus disease 2019 (COVID-19) vaccine doses worldwide. However, avoiding unacceptable toxicity with mRNA drugs and vaccines presents challenges. Lipid nanoparticle structural components, production methods, route of administration and proteins produced from complexed mRNAs all present toxicity concerns. Here, we discuss these concerns, specifically how cell tropism and tissue distribution of mRNA and lipid nanoparticles can lead to toxicity, and their possible reactogenicity. We focus on adverse events from mRNA applications for protein replacement and gene editing therapies as well as vaccines, tracing common biochemical and cellular pathways. The potential and limitations of existing models and tools used to screen for on-target efficacy and de-risk off-target toxicity, including in vivo and next-generation in vitro models, are also discussed.The field of nucleic acid therapeutics is rapidly expanding, with mRNA drug and vaccine candidates now under development for diverse indications. However, various safety concerns are associated with the mRNA platform. This Review discusses key challenges and toxicities identified during the development of mRNA drugs and vaccines, assesses models and tools used to limit toxicity, highlighting knowledge gaps and future directions.

• Publisher: Nature Publishing Group
• Subject: Coronaviruses / COVID-19 / Genome editing / Lipids / Nanoparticles / Toxicity / Vaccines