RNA interference (RNAi) is a naturally occurring post-transcriptional gene regulation process that represses the expression of specific genes. Exploiting endogenous RNAi by externally-delivered small-interfering RNA (siRNA) is a promising therapeutic for the treatment of various diseases representing several major unmet medical needs.
Researchers at the National Cancer Institute (NCI) have developed DNA- and RNA-based nanoparticles that can induce RNA interference (RNAi), molecular imaging, or a combination thereof. Two DNA- or RNA-based nanoparticles are required to induce RNAi: one nanoparticle comprising up to six (6) DNA or RNA strands and the other nanoparticle comprising the complementary DNA or RNA strands. Upon association of two complementary nanoparticles, conformational changes (or “shape switching”) occurs to both nanoparticles. Nucleic acid duplexes are released upon shape-switching, which activates functional units capable of delivering siRNA and/or transcribable DNA templates.
The National Cancer Institute is seeking statements of capability or interest from parties interested in licensing or in collaborative research to co-develop RNAi-based nanoparticle therapeutics for cancer, viral infection, and genetic diseases.
• Cancer, infectious disease, and genetic disease therapeutics
• Research tool to study cancer, viral infection, and other diseases
• Molecular imaging
• Drug delivery
• Increased potency
• Low cytotoxicity
• Tunable stability
• Multiple functionalities and targets
• Controlled activation
• Dynamic interaction or “Shape-Switching”
• Activation from only two particles for simple delivery and functionality
Bruce Shapiro (NCI), Kirill Afonin (University of North Carolina, Charlotte), Eckart Bindewald (Leidos Biomedical Research), Mathias Viard (Leidos Biomedical Research), Wojciech Kasprzak (Leidos Biomedical Research), Marina Dobrovolskaia (Leidos Biomedical Research), Justin Halman (University of North Carolina, Charlotte), Wojciech Khisamutdinov (Leidos Biomedical Research)
- U.S. Patent Filed: U.S. Patent Application Number 62/480,899, Filed 03 Apr 2017
- E-059-2009 - In silico design of RNA nanoparticles
- E-039-2012 - Nanoparticles for the targeted treatment of infected cells
- E-223-2012 - Co-Transcriptional Assembly of Modified RNA Nanoparticles
- E-765-2013 - Multifunctional RNA Nanoparticles as Cancer and HIV Therapeutics
- E-156-2014 - Nucleic Acid Nanoparticles for Triggering RNA Interference