Every time a shuttle docks with the International Space Station (ISS), a delicate dance unfolds between the shuttle’s docking system and its counterpart on the station. Thanks to international standards, these mechanisms are universally compatible, ensuring astronauts and cargo can safely and seamlessly enter the station.
A similar challenge arises at the microscopic level when lipid nanoparticles (LNPs) – the revolutionary drug delivery vehicles behind the COVID-19 vaccines – attempt to deliver mRNA to cells. Optimizing the design and delivery of LNPs can greatly enhance their ability to deliver mRNA successfully, empowering cells with the disease-fighting instructions needed to transform medicine.
Escaping the endosome
Unfortunately, even when LNPs reach their target cells, the nanoparticles are typically captured by endosomes – tiny protective sacs within the cell. If LNPs can’t escape, it’s like a shuttle getting stuck in the docking process, the safety of the station just out of reach.
If the endosomal escape process doesn’t happen, LNPs become trapped and cannot deliver therapeutic cargo. They can make it all the way from a needle into the cell, but if they don’t open that final barrier, they’re useless.”
Michael J. Mitchell, Associate Professor in Bioengineering (BE), University of Pennsylvania School of Engineering and Applied Science (Penn Engineering)
A new approach
A few years ago, researchers at Carnegie Mellon University made an intriguing discovery: adding a branch to the end of LNPs’ normally linear lipid tails dramatically improved mRNA delivery. This discovery prompted Marshall Padilla, a postdoctoral fellow in the