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Image: Courtesy of Penn Engineering
Lipid nanoparticles (LNPs), the tiny delivery vehicles for mRNA therapies, already work extremely well, as demonstrated by the COVID-19 vaccines, which saved millions of lives.
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Penn Engineering’s Michael Mitchell is the principal investigator at the Mitchell Lab.
(Image: Courtesy of Penn Engineering)
Made of different types of lipids, the same class of fatty molecules found in animal tissue and other natural substances like olive oil, LNPs have a unique ability to deliver delicate medicinal cargo. Because the membranes of animal cells are also made of lipids, the particles can easily pass through them.
But, as
Michael J. Mitchell
, associate professor of bioengineering, has found, there are still plenty of ways to improve LNPs, making them even more potent, precise and better tolerated.
Recently, the Mitchell Lab published a suite of papers in leading journals including
Nature Materials
Nature Nanotechnology
the Journal of the American Chemical Society
, and
ACS Nano
demonstrating some of the ways in which the group is modifying LNPs to advance precision medicine:
Engineered lipid nanoparticles reprogram immune metabolism for better mRNA vaccines
Postdoctoral fellow Dongyoon Kim and doctoral student Amanda Murray found that subtle changes in lipid chemistry can influence immune cell metabolism and reduce inflammation. The results suggest that LNPs can actively shape how immune cells respond, opening new avenues for vaccines and immunotherapies.
New nanoparticle could unlock universal immunotherapy for solid cancers
Postdoctoral fellows Qiangqiang Shi and Jinjin Wang and doctoral student Hannah Geisler have helped develop prodrug-tethered LNPs (pLNPs), which could one day serve as a universal immunotherapy for cancers that form solid tumors. The particle delivers both mRNA that activates immune cells and a drug that blocks tumor-driven immune suppression.
New lipid nanoparticle design improves precision of mRNA vaccine delivery
Doctoral student Hannah Yamagata and postdoctoral fellow Marshall Padilla redesigned a key LNP component to steer mRNA toward lymph nodes while reducing off-target accumulation in the liver. The advance could enable more precise, lower-dose vaccines and expand the potential of mRNA therapies for cancer and autoimmune disease.
New robotic microfluidic platform brings AI to lipid nanoparticle design
Doctoral student Andrew Hanna helped develop LIBRIS, an automated microfluidic platform that dramatically accelerates the process of synthesizing LNPs. By generating on the order of 1,000 distinct formulations per hour, the system could enable the large, systematic datasets needed to train predictive AI models, which could help researchers design particles with particular properties.
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Ian Scheffler
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