MIT Researchers Keep Experimental RNA Vaccines Stable for a Year at Room Temperature

An RNA vaccine spent a year at room temperature before researchers gave it to mice—and it still produced an immune response comparable to a vaccine using Moderna-like delivery particles. In a new Nature Biotechnology study, MIT researchers report using machine learning to find a stabilizing mixture that could ease a major obstacle to distributing RNA vaccines: their need for cold storage.

What survived storage

RNA is fragile. Lipid nanoparticles—tiny particles of fat that protect RNA and help it enter cells—make vaccines possible, but the RNA vaccines described by MIT still require storage at minus 20 to minus 80 degrees Celsius. That creates a shipping problem where cold-storage facilities are unavailable.

The team put COVID-19 vaccine RNA inside its revised particles, then removed moisture through vacuum drying. After storage at room temperature for one year or at 37 degrees Celsius for two months, the vaccines generated immune responses in mice equivalent to vaccines carried by particles similar to those in the original Moderna formulation.

That is a test of stored vaccines in mice, not a human trial. The reported comparison measures immune response; it does not establish how well a warm-stored vaccine would protect people.

How the search narrowed

The researchers had previously made more heat-resistant particles using polymers. Those particles differed slightly from formulations used in FDA-approved COVID-19 vaccines. This time, they sought to stabilize particles closer to the approved designs, but ingredients that had worked in earlier experiments were not producing the result they wanted.

They screened nearly 50 FDA-approved excipients—added ingredients such as sugars, salts or polymers—for their ability to stabilize RNA inside the particles. To check how well each worked, they delivered RNA that makes cells produce a glowing protein. More light indicated that more functional RNA had reached the cells.

From that screen, the team selected five promising ingredients. A machine-learning algorithm predicted which proportions might best stabilize Moderna-like particles. The researchers tested two mixtures at a time in cells, returned the results to the algorithm, and repeated the process until they had a candidate for animal tests. MIT says the guided search took weeks; earlier ingredient testing and screening had taken months without reaching the desired stability.

Two storage tests

01One year

Room temperature

Vacuum-dried vaccine particles were stored at room temperature for one year before the mouse immune-response test.

02Two months

37 degrees Celsius

A second group of vacuum-dried vaccine particles was stored at 37 degrees Celsius for two months before the mouse immune-response test.

A different particle needs a different ratio

The group also applied the approach to particles similar to those used for Pfizer’s COVID-19 vaccine. The stabilizing ingredients stayed the same, but their proportions changed. That distinction matters: the study presents a method for finding a suitable mixture for a given particle design, not one recipe shown to work unchanged across both designs.

The researchers say a heat-resistant formulation developed for a particular particle could be adapted to carry other types of mRNA. The mouse storage tests described here used COVID-19 vaccine RNA, so that wider application remains a proposed next use rather than a result demonstrated across vaccines.

An opening for patches

Heat tolerance could also make a solid delivery format more practical. The team used the formulation in microneedle patches containing a SARS-CoV-2 antigen. These patches release vaccine through tiny needles that dissolve in the skin, and they produced a mouse immune response similar to injectable RNA vaccines.

The storage and patch findings point to two possible benefits of the same formulation: less dependence on cold facilities and another way to give a vaccine. Both rest on early testing. The next question is whether the preserved immune response and the delivery approach hold up beyond mice.