Thermostable self-amplifying RNA formulations retain potency after 30 days at 4 °C

Cold-chain requirements constrain where RNA vaccines can be deployed.

We formulated self-amplifying RNA in a lyoprotectant-stabilised lipid shell and tracked potency across a 30-day window at 4 °C, with parallel accelerated stability at 25 °C and 40 °C.

Potency remained above 90% of the release value at 4 °C for the full 30 days, and above 78% for seven days at 25 °C. Particle size and polydispersity were unchanged within measurement error.

The mechanism appears to be sugar-mediated vitrification of the aqueous core, which reduces the molecular mobility that drives RNA hydrolysis.