Targeted delivery of siRNA into human T cells

Abstract

RNA interference (RNAi) is now increasingly being considered as a promising approach in the therapy of a variety of human diseases. However, for RNAi to become a feasible clinical application, a major obstacle is efficient delivery of 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. In recent times, antibodies to cell-surface molecules have gained prominence as a vehicle for the targeted delivery of siRNAs into specific cells. We have developed a novel approach that utilizes single chain antibody (scFv) to the pan T cell surface protein CD7, we show the specific delivery of functional siRNA into human T cells. As a proof of principle, we were able to successfully control HIV-1 replication by simple intravenous injections using scFv-CD7/9R-siRNA formulation targeting the viral RNA in humanized mice, the newest animal model that closely simulates human HIV infections. These results offered a high degree of optimism to the practical applicability of RNAi as therapy for AIDS. Thus we demonstrate the feasibility of RNAi as a therapeutic intervention for HIV-AIDS.