Poster abstracts
Poster number 34 submitted by Lili Du
Arrowtail RNA for Ligand Display on Ginger derived Exosome-like Nanovesicles to deliver siRNA for Cancer Suppression
Zhefeng Li (Center for RNA Nanobiotchnology and Nanomedicine; College of Pharmacy,The Ohio State University), Lili Du (Center for RNA Nanobiotchnology and Nanomedicine; College of Pharmacy,The Ohio State University), Hongzhi Wang (Center for RNA Nanobiotchnology and Nanomedicine; College of Pharmacy,The Ohio State University), Chad Benntt (Medicinal Chemistry Shared Resource, Comprehensive Cancer Center; The Ohio State University), Huang-ge Zhang (James Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville), Peixuan Guo (Center for RNA Nanobiotchnology and Nanomedicine; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry; College of Medicine,The Ohio State University)
Abstract:
Exosomes had shown increasing potential as delivery vesicle or therapeutic for gene therapy, but challenging like cost/yield, drug payload and targeting specificity still exist. Plant derived exosome-like nanoparticle were reported as a promising substitution and exhibit biocompatible through oral, intranasal administration. Recently, we reported the control of RNA orientation to decorate extracellular vesicles with cell targeting ligand for specific delivery of siRNA to tumors (Nature Nanotechnology, 13: 82-89, 2018). Here we introduce another application of arrowtail RNA nanoparticle to display ligand on ginger derived exosome-like nanovesicles (GDENs) for siRNA delivery and tumor inhibition through IV administration. Cushion ultracentrifugation coupled with equilibrium density gradient ultracentrifugation were used for purifying GDENs that displayed size, density and morphology similar to human derived exosome. As ligand to bind cancer, folic acid was displayed on the surface of GDENs for targeted delivery of survivin siRNA to KB cancer models. In vitro gene knockdown efficacy by folate-GDENs/siRNA complex was comparable to transfection. The observed inhibition of tumor xenograft after intravenously injection reveals the potential of GDENs as economic delivery system for siRNA.
References:
Pi F, Binzel D, Lee TJ, Li Z, Sun M, Rychahou P, Li H, Haque F, Wang S, Croce CM, Guo B, Evers BM, Guo P. Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression. Nature Nanotechnology. 2018 Jan; 13(1):82-89.
Li Z, Yin H, Wang H, Benntt C, Wang D, Zhang HG, Guo P. Arrowtail RNA for Ligand Display on Exosome-like Nanovesicles to deliver siRNA for Cancer Suppression. Under preparation.
Keywords: Exosome, RNA, FA