BME Seminar Series (Zoom): Overcoming Barriers to RNAi Delivery for Cancer Treatment Using Peptide-Based Nanocarriers

Zoom: https://uci.zoom.us/s/97629106431 Password: 198Sem

Abtract: The discovery that exogenous siRNAs induce sequence-specific inhibition of gene expression has resulted in the investigation of the use of RNAi-based approaches to treat many diseases, including cancer. Though many oncogenes have been identified as targets for gene therapy to treat cancer through siRNA delivery, some challenges must be addressed to harness the full potential of RNAi technology. siRNAs face several significant barriers to delivery that limit the efficacy of siRNA therapeutics. Intracellular trafficking of siRNAs is prevented by their hydrophilicity, high molecular weight and negative charge. Additionally, upon entering the cell, siRNAs must escape the endosome to reach their site of action in the cytosol and avoid lysosomal degradation, diminishing their therapeutic effect. As a result, the accumulation of siRNAs at their target site to a therapeutically effective level is a crucial hurdle for delivery. Extensive research has focused on non-viral delivery of synthetic siRNAs using nanoparticles due to their enhanced stability, versatility and biocompatibility. Peptide carriers have been explored to overcome nucleic acid transport barriers and have proven to be a promising approach for efficient delivery. Cell-penetrating, targeting, and fusogenic peptides are advantageous for cellular internalization, cell-specific uptake, and endosomal escape, respectively. This seminar will discuss the development and evaluation of novel peptides that have demonstrated efficient delivery of bioactive siRNAs into ovarian cancer cells and silencing of a target oncogene, resulting in decreased cancer cell migration.  

Bio: Angela Alexander-Bryant is an assistant professor in the Department of Bioengineering at Clemson University. She received her bachelor’s and master’s degrees from Johns Hopkins University in materials science and engineering and her Ph.D. in bioengineering from Clemson University. Alexander-Bryant’s Nanobiotechnology Lab is working to develop novel, clinically translatable therapeutic delivery strategies to improve targeted treatment of disease. Her research leverages materials science, nanotechnology, gene therapy and drug delivery to advance cancer therapies toward cures. She is a 2021 recipient of an Early Career Award from the National Science Foundation for her work on peptide-based delivery systems for gene therapy. Alexander-Bryant is also the director of Diversity and Inclusion in the Department of Bioengineering. In this role, she aims to increase the recruitment and retention of students from underrepresented groups into the department’s undergraduate and graduate programs.