Lipid nanoparticles for RNA delivery: COVID-19 vaccines, chemistry, and beyond
Kathryn A. Whitehead
Department of Chemical Engineering
Department of Biomedical Engineering
Carnegie Mellon University
Messenger RNA (mRNA) therapeutics have taken center stage thanks to the successful deployment of the SARS-CoV2 mRNA vaccines in hundreds of millions of people worldwide. These vaccines were made possible by a herculean effort to overcome the most significant barriers that have hindered translational efforts. Arguably, the largest challenge has been that RNA molecules do not readily enter their cellular targets within the body. This is because they are large (104 – 106 g/mol) and negatively charged; they do not have favorable biodistribution properties nor an ability to cross the cell membrane of target cells. In response to these issues, industrial and academic laboratories, including my own, have created lipid nanoparticles that spontaneously package RNA and deliver the RNA to key cellular targets in vivo. Here, I will describe biodegradable, ionizable lipid-like materials called ‘lipidoids’ that my lab has used to create RNA-loaded lipid nanoparticles that induce protein expression in a variety of tissues in mice. This talk will describe an especially potent lipid nanoparticle, its chemical characteristics that confer efficacy, and potential applications, including delivery to the pancreas. Together, these data advance our understanding of lipid nanoparticle chemistry and are expected to contribute to the successful formulation of next-generation mRNA therapies.
Kathryn A. Whitehead is a Professor in the Departments of Chemical Engineering and Biomedical Engineering (courtesy) at Carnegie Mellon University. Her lab develops drug delivery systems for RNA, proteins, and applications in maternal and infant health. She obtained bachelor and doctoral degrees in chemical engineering (Univ. of Delaware; Univ. of California, Santa Barbara) before an NIH Postdoctoral Fellowship at MIT. Prof. Whitehead is the recipient of numerous awards, including the NIH Director’s New Innovator Award, the DARPA Director’s Fellowship, and the ASEE Curtis W. McGraw Research Award. She has also received the Controlled Release Society’s Young Investigator Award and served on its Board of Directors. Prof. Whitehead is an elected Fellow of the American Institute for Medical and Biological Engineering and the Controlled Release Society. In 2021, she gave a TED talk on the lipid nanoparticles (i.e., “fat balls”) used in the COVID-19 mRNA vaccines. Her publications have been cited over 10,000 times, and her patents have been licensed and sublicensed for reagent and therapeutic use.