Poster abstracts
Poster number 60 submitted by Congcong Xu
Development of stable boiling-resistant Phi29 pRNA nanoparticles for specific targeting and treatment of cancers
Emil Khisamutdinov (College of Pharmacy; College of Medicine/Department of Physiology & Cell Biology/ Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 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, OH, USA), Daniel 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, OH, USA), Farzin Haque (College of Pharmacy; College of Medicine/Department of Physiology & Cell Biology/ Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA), Dan Shu (College of Pharmacy; College of Medicine/Department of Physiology & Cell Biology/ Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA), Congcong Xu (College of Pharmacy; College of Medicine/Department of Physiology & Cell Biology/ Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA)
Abstract:
The field of RNA nanotechnology necessitates creation of stable and tunable, functional RNA nanoparticles. We have shown that the three-way junction of bacteriophage phi29 motor pRNA has unusual stability and can self-assemble from three fragments with high efficiency, while displaying thermos and chemical stability. We have fabricated a variety of RNA architectures with precise control of shape, and stoichiometry by exploiting the flexibility of the pRNA-3WJ. The stable 3WJ was used to construct planar triangular, square and pentagon scaffolds – through the stretching of the 60o angle of the pRNA-3WJ to 90o and 108o. The resulting scaffolds were shown to be tunable in size and chemical and thermodynamic stability through simple modification of the scaffold’s core strand. Additionally, nucleotides resulted in RNA nanoparticles resistant to RNase degradation. Furthermore, all RNA scaffolds were incorporated with siRNA, ribozyme, and fluorogenic aptamers, keeping the original folding and functionalities of the RNA functional groups. RNA nanoparticles were then used for specific targeting and binding to prostate cancer, breast cancer, and glioblastoma cells through the use of RNA aptamers or chemical ligands. The RNA nanoparticles were shown to specifically target tumors in vivo with no detectable accumulation in healthy vital organs and tissues four hours post systemic injection and delivered therapeutics modules in vitro and in vivo. Furthermore, the RNA nanoparticles are non-toxic and display favorable pharmacological profiles in vivo.
References:
[1] Guo P. 2010. The emerging field of RNA nanotechnology. Nature Nanotechnology 5:833-842.
[2] Jasinski DL, et al. and Guo P. 2014. Physicochemically tunable polyfunctionalized RNA square architecture with fluorogenic and ribozymatic properties. ACS Nano. 8:7620-7629.
[3] Khisamutdinov E, et al. and Guo P. 2014. RNA as a boiling-resistant anionic polymer material to build robust structures with defined shape and stoichiometry. ACS Nano. 8:4771-4781.
[4] Khisamutdinov E, et al. and Guo P. 2014. Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles. Nucleic Acids Research.15:9996-10004.
Keywords: RNA Nanotechnology, Cancer treatment, RNA nanoparticle