Joshua A. Choe, Jacobus Burger, Jamie Jones, Apurva Panjla, William L. Murphy
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Opportunities in Therapeutic mRNA Stabilization: Sequence, Structure, Adjuvants and Vectors
The reliance of current COVID-19 mRNA lipid nanoparticles on cold storage increases the cost and reduces access to the vaccines. As therapeutic mRNA expands to other clinical opportunities, better methods to stabilize the medicines during shipping, storage, and delivery are needed. This work reviews advances in mRNA design with a focus on codon optimization, chemical modifications, and RNA structures. Additionally, technologies promoting mRNA nanoparticle stabilization including ionizable lipids, excipients, lyophilization, and inorganic systems are reviewed. Application of emerging methods to improve storage and stabilization of mRNA nanoparticles may produce stable, “off-the-shelf” mRNA therapeutics that can be accessed worldwide.
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