MIT reports RNA vaccine formulation retained activity after months of warm storage

MIT researchers say they have developed a formulation for RNA vaccine particles that remained active after two months at 37 °C or a year at room temperature. In mouse tests, the stored vaccines produced immune responses comparable to a vaccine carried by particles similar to those in an earlier Moderna formulation. The result could help address a storage problem that complicates distribution, but it has not established that a vaccine can be shipped or used without refrigeration in practice.

The team used a machine-learning algorithm to choose a mixture of ingredients that stabilize the lipid nanoparticles carrying the RNA. Its account, published by MIT News on September 28, describes laboratory screening and mouse experiments. The underlying new Nature Biotechnology paper was unavailable for this report, so details beyond MIT’s account could not be checked against the study.

How the formulation was selected

RNA is fragile, and lipid nanoparticles help protect it and deliver it into cells. The vaccines described by MIT ordinarily require cold storage, which can make transport difficult where suitable facilities are scarce. The researchers focused on improving the stability of nanoparticles similar to those used for Moderna’s COVID-19 vaccine, using added ingredients known as excipients rather than starting with an entirely new delivery system.

According to MIT, the team screened nearly 50 FDA-approved excipients. It first tested how well each candidate helped nanoparticles deliver RNA that instructs cells to make luciferase, a light-producing protein. The light emitted by the cells provided a way to measure delivery activity. Researchers then selected five promising ingredients and used the algorithm to predict useful ratios, testing two predicted mixtures at a time in cells and feeding the results back into the model.

What the storage tests showed

For the next tests, the researchers packaged COVID-19 mRNA antigens in the selected particles and vacuum-dried them. MIT reports that doses stored for two months at 37 °C, about 98 °F, or for one year at room temperature still prompted immune responses when given to mice. Those responses were comparable to responses from a vaccine using nanoparticles similar to the original Moderna formulation, according to the university.

The team also incorporated the heat-resistant formulation into solid microneedle patches carrying a SARS-CoV-2 antigen. MIT says the patches produced mouse immune responses similar to those from its injectable RNA vaccine. The researchers applied the algorithm to particles similar to those used for Pfizer’s COVID-19 vaccine as well, changing the ratios of the selected excipients for that formulation.

These comparisons measure immune response in animals. MIT’s account does not establish protection against infection, effectiveness in people, or approval of a product. It also does not show that manufacturing, shipping and use at scale can proceed without a cold chain. Those questions matter before the reported storage stability can translate into wider access.

How it fits with earlier work

A separate 2025 study in npj Vaccines reported that a different freeze-dried mRNA vaccine retained biological activity after one year at 25 °C. That candidate used newly designed lipid and RNA components. The earlier result provides a precedent for long storage at room temperature, while MIT’s reported approach focuses on adjusting the ingredients around particles resembling those already used in COVID-19 vaccines. The studies do not establish that either candidate is ready for routine distribution.

Another study, published in Drug Delivery and Translational Research, illustrates why storage claims need to measure biological function as well as the physical condition of particles. In its tests of mRNA lipid nanoparticles in microneedle patches, reporter-protein expression fell 59% during the first week at 25 °C and 87% within two days at 40 °C. The findings concern a different formulation, but show that apparently stable particle properties alone may not mean the RNA remains effective at delivering its instructions.

MIT says the Gates Foundation partly funded the new research. The immediate finding is a preclinical formulation result: dried doses remained active under the reported storage conditions and produced mouse immune responses. Whether that performance holds across manufacturing batches, distribution conditions and human trials remains unanswered in the available account.