Abstract 304: Peptide-mediated delivery of siRNAs targeting CSNK2A1 decreases migration of ovarian cancer cells in vitro

Abstract

Abstract Background Ovarian cancer (OC) is among the most commonly diagnosed cancers and combined with the low responses to therapeutics, it has the highest mortality among gynecological cancers. When diagnosed at stage III and stage IV, survival rates remain below 30%. Over 90% of ovarian cancers are epithelial-based, resulting in proliferation with both local and distant metastasis. Common modes of treatment typically include surgical debulking and platinum-based chemotherapies. However, approximately 80% of confirmed late-stage OC patients will encounter recurrence, multidrug resistance, or metastasis. As a result, there is a need for more effective treatments by means of sustainable therapeutics. RNA interference (RNAi)- based therapies via short interfering RNA (siRNA) have shown promise a potential treatment method. However, siRNAs cannot readily enter the cell due to their large size and negative charge. Thus, siRNAs must be combined with a carrier that maintains the efficacy of the therapeutic by promoting membrane interaction, internalization, and release of siRNAs. Fusogenic peptides (FPs) serve as efficient carriers by complexing with siRNAs through electrostatic interactions and mediating endosomal escape to maintain bioactivity. Here, we investigate the use of a novel FP for the delivery of siRNAS targeting CSNK2A1 and characterize ovarian cancer cell response. Methods OVCAR3 human ovarian cancer cells were treated with fusogenic peptides complexed with either non-targeting siRNAs or siRNAs targeting CSNK2A1 at varying nitrogen to phosphorus (N:P) ratios and downstream cellular analysis was conducted. Cytotoxicity of both the fusogenic peptide vehicle alone and peptide/siRNA complexes was determined using MTS assays. The effect of the peptide/siRNA complex on ovarian cancer cell migration was measured using a scratch wound healing assays. Results The FP vehicle displayed no significant decreases in cell viability at higher N:P ratios. This result indicates that the FP vehicle is not cytotoxic to the cells and demonstrate the potential biocompatibility of the delivery system. In the scratch wound healing assay, percent wound healing was substantially decreased when ovarian cancer cells were treated with peptide complexed with siRNAs targeting CSNK2A1 in contrast to treatment with peptide complexed with non-targeting siRNAs. Higher N:P ratios displayed an overall greater decrease in wound healing. In future studies, we will examine whether peptide/siRNA complexes affect the invasiveness of ovarian cancer cells. Citation Format: Anthony Hazelton, Timothy Samec, Jessica Boulos, Serena Gilmore, Angela Alexander-Bryant. Peptide-mediated delivery of siRNAs targeting CSNK2A1 decreases migration of ovarian cancer cells in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 304.