Better fat bubbles could power a new generation of mRNA vaccines

New lipid delivery systems aim to improve potency and reduce side effects

As any dietician will tell you, some fats are good—and that is surely true of the little fatty balls found in two of the world’s most widely used COVID-19 vaccines. Known as lipid nanoparticles (LNPs), these tiny bubbles of fat encase messenger RNA (mRNA) that encodes a viral protein, helping ferry it into cells and shield it from destructive enzymes. The technology was key to the success of COVID-19 shots from Moderna and the Pfizer-BioNTech collaboration. But as beneficial as these fats are, there is plenty of room for improvement.

The nanoparticles are a major source of unwanted side effects when they spread through the body, triggering the aches and inflammation many people experience after vaccination. They do a poor job of unloading their cargo once inside cells, a necessary step for the proteinmaking machinery to turn the mRNA sequences into immune-priming signals. And because they tend to fall apart when warm, they have to be stored at low temperatures, limiting their global use.

“This is a system that clearly has legs,” says biochemist Pieter Cullis of the University of British Columbia (UBC), Vancouver, who created the first LNPs, but “we still need to increase the efficiency of LNPs—that’s for sure.”

A new generation of LNPs with greater potency, fewer side effects, increased stability, and more precise tissue-targeting properties is now under development at big pharma and biotech startups. Big money is at stake: These improved nanoparticles could lead to better mRNA vaccines for COVID-19 and other diseases. They might also help mRNA deliver on its promise as a therapeutic tool to treat disease. “There are innovations on delivery that certainly could change the game,” says Philip Santangelo, a biomedical engineer at the Georgia Institute of Technology who has collaborated with several mRNA companies.

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Article by Elie Dolgin – Science