Poster abstracts
Poster number 63 submitted by Mario Vieweger
RNA Dendrimer Platform for Nanomedicine
Mario C. Vieweger (College of Pharmacy and College of Medicine, The Ohio State University), Farzin Haque (College of Pharmacy and College of Medicine, The Ohio State University), Peixuan Guo (College of Pharmacy and College of Medicine, The Ohio State University)
Abstract:
RNA nanotechnology has been rapidly advancing due to its increasing application in nanomedicine. Its functional versatility and ease of assembly allow efficient preparation of homogeneous nanoparticles with defined shape, size and stoichiometry. In therapeutics, RNA nanoparticles have shown favorable pharmacokinetic and biodistribution properties by avoiding accumulation in healthy organs and tissues with efficient retention in tumors. In order to evaluate the effects size, shape, and payload have on the therapeutic efficacy of RNA nanoparticles, we designed five generations (G0-G4) of RNA dendrimers built with the ultrastable three-way junction (3WJ) motif of bacteriophage phi29 as building block. This series of dendrimers is assembled around a central, square-shaped RNA core surrounded by an increasing number of 3WJ layers. All five generations can be efficiently self-assembled using one-pot synthesis into monodisperse globular particles with diameters ranging from 2.8 nm (G0) to 26 nm (G4). Thermal gradient fluorescence and gel electrophoresis (TGGE) reveal a bi-phasic assembly/disassembly mechanism in which the outer most layers form around a preformed thermodynamically stable core. This feature allows thermodynamic control over release and degradation of the external 3WJ strands that can be functionalized with targeting and therapeutic moieties. Upon incorporation of folate on the peripheral branches, RNA dendrimers show high binding and internalization into cancer cells. RNA dendrimers are envisioned to have a major impact in targeting, disease therapy, molecular diagnostics and bioelectronics in the near future.
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. Sharma A, Haque F, Pi F, Shlyakhtenko LS, Evers BM, Guo P. Controllable Self-assembly of RNA Dendrimers. Nanomedicine: Nanotechnology, Biology, and Medicine. 12:835–844 (2016).
Keywords: RNA Nanotechnology, Dendrimers, Therapeutics