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 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 of phi29 DNA packaging motor, RNA nanoparticles were constructed by bottom-up self-assembly containing the anti-PSMA aptamer as targeting ligand and anti-miR17 or anti-miR21 as therapeutic modules. The 16 nm 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.Molecular Therapy (2016); doi:10.1038/mt.2016.85.
Molecular therapy : the journal of the American Society of Gene Therapy. 2016 Apr 29 [Epub ahead of print]
Daniel W Binzel, Yi Shu, Hui Li, Meiyan Sun, Qunshu Zhang, Dan Shu, Bin Guo, Peixuan Guo
College of Pharmacy, Department of Physiology & Cell Biology, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA., Nanobiotechnology Center, Markey Cancer Center and Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, USA., College of Pharmacy, Department of Physiology & Cell Biology, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA., Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA., Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA., College of Pharmacy, Department of Physiology & Cell Biology, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA., Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA., College of Pharmacy, Department of Physiology & Cell Biology, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.