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Biomedical, Biotechnology

Fusogenic Peptides for Delivery of RNAi Therapeutics to Ovarian Cancer

Inventors: Dr. Angela Alexander-Bryant Dr. Timothy Samec

Market Overview

Epithelial ovarian cancer is the 5th leading cancer among women, with a 49% five-year survival rate. Current treatment strategies for ovarian cancer include surgical removal, chemotherapy, and radiation; however, these treatments often prove ineffective or toxic to patients. Global News Wire expects the nanotechnology drug delivery market to have an 18.7% CAGR growth rate from 2022 to 2032. Current chemotherapies are limited due to the toxicity of therapeutic and resistance to treatment. Furthermore, there has been increased attention to reducing systemic effects and therapeutic concentration. This technology fills this gap by providing an effective delivery platform for RNA interference (RNAi) therapeutics, a mechanism that can be used to silence oncogenes responsible for cancer progression. While a promising strategy for treatment, RNAi cargo requires an efficient delivery system to improve its bioavailability and delivery into cancer cells. Clemson University researchers have developed novel fusogenic peptides that facilitate efficient uptake and endosomal escape of RNAi therapeutics in ovarian cancer cells, resulting in enhanced bioactivity  and therapeutic efficacy.

Applications:

Gene silencing for cancer treatment

Technical Summary:

The peptides' design is composed of alternating residues of hydrophobic and hydrophilic amino acids, highlighted by repeating aspartic acid residues. Due to the inclusion of a cationic tail, these peptides have shown effective electrostatic complexation and protection of RNAi cargo. High biocompatibility and cellular internalization have been shown both in vitro and in vivo. These sequences have proven to enhance endosomal escape through the protonation of hydrophobic amino acids, which leads to a conformational change in a more acidic pH to disrupt the endosomal membrane. Upon release from the endosome, the siRNA is released into the cytoplasm of the cell, where it is bioactive. Due to this enhanced cytoplasmic delivery, gene silencing studies have proven the system's significant efficacy in silencing the target oncogene, resulting in significant antitumor activity in vivo. Therefore, these novel peptides demonstrate a highly efficient delivery system for RNAi therapeutic applications for cancer treatment.

Advantages:

  • Facilitates endosomal release of cargo, increasing the bioavailability of therapeutic
  • Electrostatic complexation of cargo, resulting in a wide range of potential cargo
  • High biocompatibility and tumor localization, lower adverse systemic effects compared to current treatments

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Technology Overview

State of Development

Preclinical and invivo proof of concept

Patent Type

PCT

Category

Biomedical, Biotechnology

Serial Number

US2023/061436

CURF Reference No.

2021-025

Inventors

Dr. Angela Alexander-Bryant Dr. Timothy Samec


For More Info, Contact:

A. Chris Gesswein
Executive Director
E: agesswe@clemson.edu
P: (864) 656-0797

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