Site-specific drug delivery has always been a challenge in gene therapy. It is urgently required to develop a new system to overcome the off-target effect, low efficiency and high toxicity of the currently available approaches. Recently, small interfering RNA (siRNA) is emerging as a promising therapeutic drug against a wide array of diseases. Current techniques for siRNA transfer use viruses or synthetic agents as delivery vehicles. However, these approaches are toxic and low-efficient, and more importantly, can not deliver siRNA to specific tissues and organs.

To better deliver the siRNA and other drugs, we are trying to construct a novel system which employs MVs to encapsulate and protect siRNAs for delivery to target cells. Microvesicles (MVs) are lipid bilayer vesicles which are naturally secreted by almost all cell types, playing crucial roles in intercellular transport of bioactive molecules, including siRNAs. Given the intrinsic ability to traverse biological barriers and to naturally transport functional siRNAs between cells, MVs potentially represent a novel and exciting drug carrier for therapeutic uses. Thus, MVs derived from cells engineered to express siRNAs may be capable of delivering siRNAs to local cellular environment.

To achieve site-specific siRNA delivery, we will express targeting protein onto the surface of MVs and the modified MVs will, in theory, have the ability to target specific tissues and organs. By transfecting the producer cells with siRNA plasmids and collect MVs, we will fill the MVs with therapeutic siRNAs.

Our modified MVs are just like the “biomissile”, which can be delivered to specific cells and destroy target mRNAs. Our project will open up avenues for therapeutic applications of MVs as biomissile.