MIT engineers said on September 28, 2026 that they used a machine-learning algorithm to design lipid nanoparticle formulations that keep RNA vaccines stable without ultracold storage, reporting the work in Nature Biotechnology.
What the researchers report
According to MIT, the team adjusted the formulation surrounding the lipid nanoparticles (LNPs) typically used to deliver mRNA vaccines, producing vaccines that remained stable at room temperature for up to a year, or at nearly 100 degrees Fahrenheit for two months.
MIT said RNA-LNP vaccines currently need to be kept at -20 to -80 degrees Celsius, which makes it difficult to ship them to regions without cold-storage facilities. The institute said the work targeted the FDA-approved formulations used for the Moderna and Pfizer Covid-19 vaccines rather than the modified polymer-stabilized particles the same labs had developed earlier.
The paper, titled "Accelerated discovery of thermostable mRNA–lipid nanoparticle vaccines using data-efficient AI," appears in Nature Biotechnology, with Ana Jaklenec and Robert Langer as senior authors and graduate student Jinbi Tian and postdoc Khanh Tran as lead authors.
How the AI algorithm was used
Working with researchers at MIT's Computer Science and Artificial Intelligence Laboratory, the team developed an algorithm able to make predictions from very small datasets, MIT said. The researchers analyzed nearly 50 FDA-approved excipients, first measuring how well each stabilized RNA by delivering mRNA encoding firefly luciferase into cells and measuring emitted light.
They then selected five of the most promising excipients and used the algorithm to predict stabilizing ratios, testing two formulations at a time in cells and feeding results back into the model. MIT said the process took only a few weeks.
"The real beauty of this algorithm is that we can use it with small data sets," said Jaklenec, a principal investigator in MIT's Koch Institute for Integrative Cancer Research. Tran said that before the AI algorithm was implemented, the team spent several months on combinations and prescreening without reaching full stability.
Mina Konakovic Lukovic, a CSAIL assistant professor and an author of the paper, said the algorithm converged on a stable formulation in just a handful of iterations rather than requiring an exhaustive search.
Animal results and further formulations
MIT said the particles were used to package Covid-19 mRNA antigens, dehydrated by vacuum drying, then stored at 37 degrees Celsius for two months or at room temperature for one year. Mice vaccinated after that storage showed immune responses equivalent to mice given vaccines carried by LNPs similar to the original Moderna formulation, according to MIT.
The team also made solid microneedle patches delivering a SARS-CoV-2 antigen that MIT said produced an immune response similar to the injectable RNA vaccines. The researchers said the algorithm could also stabilize other LNP formulations, including one similar to those Pfizer uses, with the same excipients at a different ratio.
The research was funded in part by the Gates Foundation, MIT said.
Key facts and where they come from
- The formulations remained stable at room temperature for up to a year, or at nearly 100 degrees Fahrenheit for two months.
they formulated vaccines that could remain stable even when stored at room temperature for up to a year, or at nearly 100 degrees Fahrenheit for two months
- Existing RNA-LNP vaccines require storage at -20 to -80 degrees Celsius.
these RNA-LNP vaccines still need to be kept cold (-20 to -80 degrees Celsius)
- The team screened nearly 50 FDA-approved excipients and narrowed to five.
The researchers used this algorithm to analyze nearly 50 FDA-approved excipients.
- Mice given the stored vaccines showed equivalent immune responses to a Moderna-like LNP formulation.
Mice that were vaccinated with these particles, even after long-term storage, showed equivalent immune responses to mice that received vaccines carried by LNPs similar to the original Moderna formulation.
- The results are published in Nature Biotechnology with Jaklenec and Langer as senior authors.
Jaklenec and Robert Langer, the David H. Koch Institute Professor, are the senior authors of the paper, which appears today in Nature Biotechnology.
- Microneedle patches made with the formulation delivered a SARS-CoV-2 antigen.
The researchers also used their new heat-resistant formulation to create solid microneedle patches that could deliver a SARS-CoV-2 antigen.
- The work was funded in part by the Gates Foundation.
The research was, in part, funded by the Gates Foundation.