RNAi Therapeutics: In vivi application

Abstract

RNA interference (RNAi) is now increasingly being considered as a promising approach in the therapy of a variety of human diseases including cancers, viral infections, degenerative diseases, and inflammation, to name a few. 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 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. First, we have used a Rabies virus glycoprotein derived peptide as ligand for delivery mediated by binding to its cognate receptor expressed on neuronal cells. As a second approach, we have used a single chain antibody directed to the pan T cell molecule, CD7 for specific delivery to T cells. We demonstrate the viability of both approaches in delivering siRNA and bringing about effective target gene silencing in animal models.