2021 Research Conference

Kathryn Whitehead, PhD, Associate Professor, Carnegie Mellon University

Kathryn A. Whitehead is an Associate Professor and Dean’s Career Fellow 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 Ruth L. Kirschstein 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 was named as a Pioneer on the MIT Technology Review’s Innovators Under 35 list and as one of the Brilliant Ten by Popular Science. Most recently, she gave a TED talk on the lipid nanoparticles (i.e., “fat balls”) used in the in the COVID-19 mRNA vaccines. Her publications have been cited over 7,000 times, and several of her patents have been licensed and sublicensed for reagent and therapeutic use.

Lipid nanoparticles for RNA Delivery: SARS-CoV-2 vaccines, chemistry, & beyond

Messenger RNA (mRNA) therapeutics have been thrust into the limelight, thanks to the
early, positive clinical trial news on a SARS-CoV2 vaccine from Pfizer/BioNTech and Moderna.
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 cellular 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 RNAloaded lipid nanoparticles that induce protein expression in mice. Lipidoids efficiently manipulate
gene expression in a variety of biological systems, including the liver, the lungs, and immune cells.
This talk will describe an especially potent lipid nanoparticle, its chemical characteristics that
confer efficacy, and potential applications. Together, these data advance our understanding of lipid
nanoparticle chemistry and are expected to contribute to the successful formulation of future
generations of mRNA therapies.