Weissman helped wrap mRNA in protective nanoparticles

Person: Drew Weissman
Lived: b. 1959
Field: Immunology
From: American

The story

Modifying the bases of messenger RNA solved the problem of inflammation, but another challenge remained. mRNA is a fragile molecule that the body breaks down quickly, and it needs help getting inside cells, where it can be read to make proteins. The Nobel committee notes that lab-made mRNA was long considered unstable and difficult to deliver, requiring sophisticated lipid carrier systems to encapsulate it.

Scientists had worked on that problem for decades. As early as 1978 researchers delivered mRNA into cells inside liposomes, tiny bubbles made of fatty molecules. Philip Felgner later created positively charged lipids that captured nucleic acids more efficiently, and the laboratory of Pieter Cullis at the University of British Columbia developed ionizable lipids, which made lipid nanoparticles both effective and less toxic. Biotech companies then screened many more lipids to improve them further.

Drew Weissman and Katalin Karikó brought this delivery technology together with their modified mRNA. They developed a technique for packaging mRNA in lipid nanoparticles, which protect the molecule until it reaches the desired part of the body, and demonstrated that the system worked in animals. According to the Lasker Foundation, in 2015 Norbert Pardi, a postdoctoral fellow in Weissman's laboratory, showed that lipid nanoparticles had strong potential for clinical use. Around 2017 a Zika virus vaccine candidate built on modified mRNA and this delivery system gave rapid, lasting immunity in mice and monkeys after a single dose.

When SARS-CoV-2 emerged, the pieces were in place. The Nobel committee credits the combination of base-modified mRNA, efficient delivery systems, a stabilised version of the viral spike protein and huge investment by industry and governments with making possible the two highly successful mRNA vaccines approved in late 2020.

Lipid nanoparticles have since become a standard part of mRNA medicine. Combined with base modification, they turn a short-lived molecule into a practical vaccine that prompts the body to make a viral protein and trains the immune system against it, and Weissman's laboratory now uses the same approach to explore gene editing and new treatments.