Grant: Project Grant

The COVID-19 pandemic, despite the tremendous burdens it has placed on society, brought to the forefront of medicine a new kind of drug - ribonucleic acid (RNA) medicines. The use of RNA, in particular mRNA molecules that provide instructions to human cells to make a specific protein, as drugs has been an active area of research for some time, but has only recently achieved global recognition with the approval of the COVID-19 mRNA vaccines from Pfizer and Moderna. Such vaccines, and indeed any drug that employs an RNA molecule, require a drug delivery mechanism, both to carry the RNA molecule to our cells and then to release the RNA once safely inside the cell. Lipid nanoparticles (LNP) are nano-sized bubbles that have been engineered to safely and efficiently perform this task. LNP are one of the key innovations that has allowed RNA medicines to gain traction for clinical applications. LNP are composed of multiple types of lipid species. Each component plays a specific function within the LNP. Decades of research have made step-wise improvements to LNP performance, with each iteration providing an LNP formulation that is slightly more effective or safer than its predecessor. As the leading pioneer of LNP technology, Dr. Cullis and his research group continue to make significant advances in their ability to engineer LNP for use in RNA medicines. Recently, Dr. Cullis's group discovered a structural alteration to LNP that increases the effectiveness of mRNA delivery to cells by as much as 100-fold over previously used formulations. This remarkable discovery is a significant step towards our ability to rationally design better LNP as opposed to simply screening many formulations. Ultimately, rational design will speed up the process of drug development. The purpose of this research program is to better characterize, understand, and apply this 'next-generation' LNP formulation in order to enable new and better RNA medicines in the future.