New molecules, inspired by space shuttles, advance lipid nanoparticle delivery for weight control

Penn Engineering researchers have invented a new way to synthesize the key chemical components of lipid nanoparticles that help protect and deliver medicinal payloads.

Inspired by the design of space shuttles, Penn Engineering researchers have invented a new way to synthesize a key component of lipid nanoparticles (LNPs), the revolutionary delivery vehicle for mRNA treatments including the Pfizer-BioNTech and Moderna COVID-19 vaccines, simplifying the manufacture of LNPs while boosting their efficacy at delivering mRNA to cells for medicinal purposes.

Microscopic view of lipid nanoparticles.
Like space shuttles using booster rockets to breach the atmosphere, lipid nanoparticles equipped with the new molecule more successfully deliver medicinal payloads. (Image: Courtesy of Penn Engineering)

In a paper in Nature Communications, Michael J. Mitchell, associate professor in the Department of Bioengineering, describes a new way to synthesize ionizable lipidoids, key chemical components of LNPs that help protect and deliver medicinal payloads. Mitchell and his coauthors tested delivery of an mRNA drug for treating obesity and gene-editing tools for treating genetic disease.

The method involves combining three chemicals: an amine “head,” two alkyl epoxide “tails,” and two acyl chloride “branched tails.” The completed lipidoid’s resemblance to a space shuttle strapped to two booster rockets is not coincidental: in college, says Han, a documentary about the space shuttle left him impressed with the design of solid rocket boosters that enabled the shuttle to enter orbit. “I figured that we could append two branch tails as ‘boosters’ into the lipidoid to promote the delivery of mRNA,” he says.

The addition of the branched tails led to a striking increase in the ability of LNPs equipped with the new lipidoid to deliver mRNA to target cells, much like a rocket whose boosters allow it to more easily penetrate the atmosphere. “We saw a dramatic increase of a hormone that regulates metabolism to target cells after delivering mRNA using these lipidoids, which is really exciting when you consider it as a way to treat obesity,” says Mitchell.

This story is by Ian Scheffler. Read more at Penn Engineering Today.