Poster abstracts
Poster number 54 submitted by Dan Shu
RNA Nanotechnology for Specific Delivery of Anti-miRNA for Suppression of Breast, Prostate and Brain Cancer
Dan Shu, Daniel Binzel, Hongran Yin, Hui Li (Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, College of Medicine/Department of Physiology & Cell Biology, Dorothy M. Davis Heart and Lung Institute, The Ohio State University, C), Tae Jin Lee, Carlo M. Croce (Department of Cancer Biology and Genetics, College of Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210), Yi Shu, Ren Xu (Markey Cancer Center, College of Pharmacy, University of Kentucky, Lexington, KY 40506), Bin Guo (Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102), Peixuan Guo (Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, College of Medicine/Department of Physiology & Cell Biology, Dorothy M. Davis Heart and Lung Institute, The Ohio State University, Colu)
Abstract:
MicroRNAs(miRNAs) are non-coding RNA molecules that regulating post-transcriptional gene expression and cellular differentiation, proliferation and apoptosis. The oncogenic microRNA-21 gene(miR-21) has been identified commonly overexpressed in solid tumors such as breast, lung, prostate, colon, brain cancers etc. Knocked down miR-21 expression by anti-miR21 has been proposed to treat solid tumors by up-regulating tumor suppressors, PTEN and PDCD4. However, delivery of anti-miR21 to the tumor without collateral damage requires an efficient and robust platform. Here, we report the application of RNA nanotechnology using three-way-junction(3WJ) nanoparticles derived from phi29 DNA packaging motor for specific delivery of anti-miR21 and to inhibit the growth of breast cancer, prostate cancer and brain cancer. Utilizing the thermodynamic ultra-stable 3WJ motif, multivalent RNA nanoparticles were constructed incorporating target ligands (such as folate or PSMA and EGFR RNA aptamers) and high thermodynamic stable anti-miR21 seed as therapeutic module. The RNase resistant and thermos-dynamically stable RNA nanoparticles remained intact after systemic injection in mice and strongly bind to tumors with little accumulation in health organs eight hours’ post-injection. The use of 20nM RNA nanoparticles with 54nt 3WJ, 8nt anti-miRNA seed and 30-40nt RNA targeting aptamers will enhance tumor regression effect. RNA nanotechnology exhibits clinical potentials as a platform for targeted cancer treatment.
References:
1. Guo P. The emerging field of RNA nanotechnology. Nature Nanotechnology. 2010. 5:833-42.
2. 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.
3. Shu D, Li H, Shu Y, Xiong G, Carson III WE, Haque F, Xu R, Guo P. Systemic Delivery of anti-miRNA for supression of Triple Negative Breast Cancer utlizing RNA Nanotechnology. ACS Nano. 2015. 9: 9731-9740
4. Lee TJ, Yoo JY, Shu D, Li H, Zhang J, Yu J-G, Jaime-Ramirez AC, Acunzo M, Romano G, Cui R, Sun H-L, Luo Z, Old M, Kaur B, Guo P, Croce CM, RNA nanoparticle based targeted therapy for glioblastoma through inhibition of oncogenic miR-21. Molecular Therapy. 2016.
Keywords: MicroRNAs, Breast Cancer, Prostate Cancer, Brain Cancer, RNA Nanotechnology