Poster abstracts

Poster number 6 submitted by Daniel Binzel

RNA Nanotechnology for the Specific Targeting and Delivery of miRNA for Inhibition of Prostate Cancer

Daniel W. Binzel (College of Pharmacy; College of Medicine/Department of Physiology Cell Biology/Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.), Yi Shu (Nanobiotechnology Center; Markey Cancer Center; Department of Pharmaceutical Sciences; University of Kentucky, Lexington, KY 40536, USA), Hui Li (College of Pharmacy; College of Medicine/Department of Physiology Cell Biology/Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.), Meiyan Sun (Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA), Bin Guo (Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA), Peixuan Guo (College of Pharmacy; College of Medicine/Department of Physiology Cell Biology/Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.)

Abstract:
Both siRNA and miRNA can serve as powerful gene silencing reagents but their specific delivery to cancer cells in vivo without collateral damage to healthy cells remains challenging. We report here the application of RNA nanotechnology using the three-way junction motif (3WJ) from the phi29 DNA packaging motor packaging RNA for specific and efficient delivery of anti-miRNA seed-targeting sequence to block the growth of prostate cancer in mouse models. Utilizing the thermodynamically ultra-stable three-way junction of the pRNA, RNA nanoparticles were constructed by bottom-up self-assembly containing the anti-Prostate Specific Membrane Antigen aptamer as targeting ligand and anti-miR17 or anti-miR21 as therapeutic modules. The RNase resistant and thermodynamically stable RNA nanoparticles remained intact after systemic injection in mice and strongly bound to tumors with little or no accumulation in healthy organs 8 hr post-injection, and subsequently repressed tumor growth at low doses with high efficiency.

References:
1. Guo P. The emerging field of RNA nanotechnology. Nature Nanotechnology. 2010. 5:833-42.
2. Shu D, Shu Y, Haque F, Guo P. Thermodynamically stable RNA three-way junction for constructing multifunctional nanoparticles for delivery of therapeutics. Nature Nanotechnology. 2011. 6:658-67.
3. Binzel DW, Shu Y, Li H, Sun M, Zhang Q, Shu D, Guo B, Guo P. Specific Delivery of miRNA for High Efficient Inhibition of Prostate Cancer by RNA Nanotechnology. Molecular Therapy. 2016. 4:1267–1277.

Keywords: RNA nanotechnology, Prostate Cancer, Phi29