New formulation helps RNA vaccines withstand high temperatures

MIT engineers tackled the cold‑chain limitation of mRNA vaccines by using a data‑efficient AI algorithm to redesign the lipid nanoparticle (LNP) formulations that protect and deliver RNA. They screened nearly 50 FDA‑approved excipients with an mRNA luciferase reporter to measure protection, selected five promising additives, and used the AI to predict optimal ratios. Iterative testing of two formulations at a time let the algorithm converge in a few weeks rather than months of exhaustive experimentation, and the approach generalized to LNPs similar to both Moderna and Pfizer platforms.

The optimized, polymer‑stabilized LNPs were vacuum‑dried and remained stable at room temperature for up to a year or at ~37 °C for two months. Mice vaccinated with these stored formulations generated immune responses equivalent to those from a Moderna‑like mRNA vaccine; solid microneedle patches made with the same formulation produced comparable immunity as well. The work, led by Langer and Jaklenec and reported in Nature Biotechnology, demonstrates a practical path to thermostable mRNA vaccines and adaptable delivery formats, enabling wider distribution and new applications for RNA therapeutics. The project received partial funding from the Gates Foundation.