Poster abstracts

Poster number 41 submitted by Daniel Jasinski

Development of Stable Boiling-Resistant RNA Nanoparticles for Materials Science and Nanomedicine Applications

Daniel L. Jasinski (College of Pharmacy, Department of Physiology Cell Biology, College of Medicine, and Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio), Emil Khisamutdinov, Hui Li, Daniel Binzel, Farzin Haque, Dan Shu (College of Pharmacy, Department of Physiology Cell Biology, College of Medicine, and Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio), Ren Xu (Department of Pharmacology and Nutritional Sciences, Markey Cancer Center, University of Kentucky, Lexington, KY), Tae-Jin Li, Carlo Croce (Department of Molecular Virology, Immunology and Medical Genetics, the Wexner Medical Center, The Ohio State University, Columbus, OH), Peixuan Guo (College of Pharmacy, Department of Physiology Cell Biology, College of Medicine, and Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio)

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 high thermo and chemical stability. Additionally, pRNA is a stable RNA molecule that can be functionalized with palindrome sticky-end motifs and kissing-loop motifs to form higher order RNA nanostructures. We have fabricated a variety of RNA architectures with precise control of shape, size, 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, chemical and thermodynamic stability through simply modifying the scaffold’s core strand. Additionally, the triangular RNA nanoparticles were shown to be boiling-resistant as they were stable at 100 oC, while also producing hexagonal array patterns. Using 2’-F modified nucleotides resulted in RNA nanoparticles resistant to RNase degradation. Furthermore, all RNA scaffolds were functionalized with siRNA, ribozyme, and fluorogenic aptamers, maintaining authentic folding of both nanoparticle and functional modules. 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 wer specifically targeted tumors in vivo with no detectable accumulation in healthy organs 3 hours post systematic injection. Furthermore, RNA nanoparticles are non-toxic and display favorable pharmacological profiles in vivo.

References:
1.    Guo, P. The emerging field of RNA nanotechnology. Nature nanotechnology 2010, 5, 833-842.
2.    Shu, D.; Shu, Y.; Haque, F.; Abdelmawla, S.; Guo, P. Thermodynamically stable RNA three-way junction for constructing multifunctional nanoparticles for delivery of therapeutics. Nature nanotechnology 2011, 6, 658-667.
3.    Jasinski, D. L.; Khisamutdinov, E. F.; Lyubchenko, Y. L.; Guo, P. Physicochemically Tunable Polyfunctionalized RNA Square Architecture with Fluorogenic and Ribozymatic Properties. ACS Nano 2014. 8(8):7620-9.
4.    Khisamutdinov, E. F.; Jasinski, D. L.; Guo, P. RNA as a Boiling-Resistant Anionic Polymer Material To Build Robust Structures with Defined Shape and Stoichiometry. ACS Nano 2014. 8(5):4771-81.

Keywords: RNA nanotechnology, Bacteriophage phi29, pRNA-3WJ