Frontiers in Oncology Seminars

Charge Altering Releasable Transporters: A New Class of Gene Delivery Agents for Cancer⁣⁣

Robert Waymouth, PhD⁣⁣
Tuesday, November 17, 2020⁣⁣

Robert Waymouth is the Robert Eckles Swain Professor of Chemistry at Stanford University. He was a postdoctoral fellow with the late Professor Piero Pino at the ETH in Zurich in 1987 and joined the faculty at Stanford as an Assistant Professor in 1988. He received the Alan T. Waterman Award from the NSF in 1996, the Cooperative Research Award in Polymer Science in 2009, and EPA's Presidential Green Chemistry Challenge Award in 2012 with Dr. James Hedrick of IBM Almaden. He has won several university teaching awards, including the Walter J. Gores Award, the Phi Beta Kappa Teaching Award, and is a Bass Fellow in Undergraduate Education. His research interests include the development of novel catalytic polymerization strategies and the design of functional macromolecules for applications in biology and medicine. His group has developed a new concept for gene delivery based on a class of dynamic oligomeric cationic materials that are designed to self-assemble with polyanionic nucleotides to form coascervate nanoparticles. These Charge-Altering Releasable Transporters (CARTs) are structurally unique oligomers that operate through an unprecedented mechanism, serving initially as oligo (α-amino ester) cations that complex, protect and deliver mRNA, and then change physical properties through a degradative, charge-neutralizing intramolecular rearrangement, leading to intracellular release of functional mRNA and highly efficient protein expression, both in cell culture and in live mice. In collaboration with Profs. Paul Wender and Ronald Levy, his group has shown that CARTs represent a non-toxic way to deliver protein-encoding mRNA to immune cells in living animals, providing two complementary strategies for cancer vaccination. ⁣⁣