Strategies to reduce the risks of mRNA drug and vaccine toxicity.

Strategies to reduce the risks of mRNA drug and vaccine toxicity.

Publication date: Jan 23, 2024

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.

Concepts Keywords
Discov Administration
Drugs Concerns
Nanoparticle Drug
Transformative Formulated
Vaccine Lipid
Models
Mrna
Nanoparticles
Reduce
Risks
Target
Toxicity
Transformative
Vaccine
Vaccines

Semantics

Type Source Name
disease VO vaccine
disease MESH coronavirus disease 2019
disease IDO production
disease VO route of administration
disease IDO cell
disease VO gene

Original Article

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