ArticleNPJ vaccines2026
Next-generation mRNA vaccines: strategies to overcome stability challenges.
Article in NPJ vaccines, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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0 citing papers in PubMed.
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Authors and funding
2 authors.
Funding
Abstract
Messenger RNA (mRNA) vaccines represent a paradigm shift in rapid vaccine development and pandemic preparedness, enabling unprecedented speed in antigen design and scalable, cell-free manufacturing. Despite proven clinical efficacy, widespread mRNA vaccine deployment remains critically constrained by fundamental molecular instability requiring ultra-cold chain storage. The chemical lability of the RNA phosphodiester backbone, 2'-hydroxyl-mediated transesterification, oxidative nucleobase damage, and lipid nanoparticle (LNP) structural vulnerabilities collectively limit long-term stability and the feasibility of global distribution. This review provides a mechanistic analysis of RNA hydrolysis, oxidative degradation, lipid peroxidation, PEG-lipid desorption, and freeze-thaw-induced nanoparticle aggregation, linking molecular instability to translational challenges in storage and supply chain logistics. We critically evaluate engineering strategies to enhance stability, including optimized LNP architectures, lyophilization with vitrifying excipients, antioxidant incorporation, lipid-polymer hybrid nanocarriers, hydrogel-based depots, self-amplifying mRNA (saRNA), and circular RNA (circRNA) constructs. Stability modeling, cold-chain risk analysis, and regulatory Chemistry, Manufacturing, and Controls (CMC) considerations are discussed to contextualize formulation robustness within real-world distribution systems. Advancing mRNA vaccines beyond ultra-cold dependence will require coordinated innovation in RNA engineering, delivery system optimization, and scalable manufacturing to enable thermostable, resilient, and globally deployable vaccine technologies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.