Targetede delivery of siRNA in vivo

Abstract

Background: RNA interference (RNAi) is increasingly being considered as a promising approach in the therapy of a variety of human diseases including cancers, viral infections, degenerative diseases, and inflammation. However, for RNAi to become a feasible clinical application, a major obstacle is efficient delivery of small interfering RNAs (siRNA) to specific target cells and tissues. Targeted delivery of siRNA is essential for maximizing the efficiency of gene-silencing while reducing unwanted side effects. We demonstrate two methods for the delivery of siRNA to two different target cell types in animal models, via neurons and T cells, primary cells that are extremely resistant to transfection with nucleic acids. Methods: Rabies virus glycoprotein (RVG) derived peptide was used as a ligand for neuronal cell specific delivery mediated by its binding to the alpha 7-subunit of nicotinic acetylcholine receptor. Along the same lines, a single chain antibody (scFvCD7) directed to the pan T cell molecule, CD7 was used for specific siRNA delivery to human T cells. The siRNA binding was enabled by poly 9-Arginine conjugated to the targeting moiety. Results and Discussions: RVG-9R specifically delivered siRNA into neuronal cells and prevented CNS infection with Japanese encephalitis virus in mice. scFvCD7-9R delivered siRNA specifically to human T cells and controlled HIV infection in humanized mice. Thus we have successfully targeted 2 important target cell types for the cell-specific delivery of siRNA and possibly DNA and drugs as well. Part of this work supported by Korea Ministry of Education and Science Technology (MEST)