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Revision as of 21:32, 25 September 2013
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Overview
Biomissile 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. siRNA functions through the RNA interference pathway. Normal double-stranded RNA is first processed by Dicer and Argo to become short double-stranded RNA, which is about 21-25bp in length. Then it will recruit other proteins to become RISC( RNA induced silencing complex). One of the two RNA stands in the RISC will be degraded and the remaining strand can specifically recognize other mRNA by base pairing. Once the RISC bind to other complementary mRNA, it will destroy the mRNA through the RNAi pathway. By designing siRNA against certain virus genes, we can use siRNA as molecular medicine for anti-virus treatment. Current techniques for siRNA transfer use viruses or synthetic agents as delivery vehicles. However, these approaches are toxic and low-efficient, and more importantly, they 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 exosomes to encapsulate and protect siRNAs for delivery to target cells. Exosomes 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, exosomes potentially represent a novel and exciting drug carrier for therapeutic purpose. Thus, exosomes derived from cells engineered to express siRNAs may be capable of delivering siRNAs to local cellular environment. To achieve site-specific siRNA delivery, we are trying to engineer a fusion protein which can recognize certain receptors onto the surface of exosomes, and the modified exosomes will, in theory, have the ability to target specific tissues and organs. By transfecting the HEK 293T cells with siRNA plasmids and collect exosomes, we will fill the exosomes with therapeutic siRNAs. And via the engineering of the target protein, we also endow the exosomes with the site-specific targeting ability. Our modified exosomes are just like the ‘biomissiles’, which can be delivered to specific cells and destroy target mRNAs. Our project will open up avenues for therapeutic applications of exosomes as biomissile.
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