Immunomodulation with Dynamic Nucleic Acid Nanomaterials
The University of North Carolina at Charlotte, Charlotte, NC
Department of Chemistry
Friday, September 20 – 11:00am – EB1 1011
ABSTRACT:
Therapeutic nucleic acids are being increasingly considered for the treatment of various diseases. Despite the recent approval by the FDA of the very first RNA interference-based therapy, several other promising therapeutic nucleic acids have been withdrawn from clinical trials due to severe cytokine storm. To address these barriers, more sophisticated formulations that employ rationally designed RNA molecules and their analogs are being investigated. By constructing nanoscaffolds from nucleic acids it becomes possible to precisely incorporate various therapeutic moieties such as siRNAs, aptamers, small molecules, and proteins while controlling the overall physicochemical properties of novel formulations. However, interactions between these nanoassemblies and the human immune system must be defined to permit the successful translation of this technology to the clinic. To address the fundamental questions regarding the immune recognition of these novel nanomaterials, we have designed a comprehensive study in which features such as size, shape, composition, and physicochemical properties of RNA and DNA nanoassemblies were related to their post-transfection responses in human immune cells (PBMC). The biomarkers of a pro-inflammatory response were cytokines and type I interferons. This work has become instrumental in bridging the rapidly narrowing gap between basic research on nucleic acid nanomaterials and advanced pharmaceuticals containing these novel materials.
Research reported in this presentation was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM120487. The study was also supported in part by federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
BIO:
Chemistry of Natural Compounds in 2003 and received a Ph.D. in Photochemistry from Bowling Green State University in 2008. He also obtained a Graduate Certificate in Bioinformatics, Proteomics/Genomics from a joint program between Bowling Green State University, the Medical University of Ohio, and the University of Toledo, Ohio. In the following three years, he completed a Postdoctoral Fellowship in Biochemistry at the University of California Santa Barbara (UCSB). In 2011, he was invited to take a position as Research Fellow in the Nanobiology Program at the National Cancer Institute (NCI), where I established and managed an experimental branch within the Computational RNA Structure Group. In 2015, Dr. Afonin joined UNC Charlotte as a tenure-track Assistant Professor and was promoted to the Associate Professor in 2019. Dr. Afonin is a two-time recipient of NIH Fellows Award for Research Excellence (FARE), Elected Full Member of Sigma Xi, Vice-President and Founding Council Member of the International Society of RNA Nanotechnology and Nanomedicine, and a recipient of several NIH funding awards.