Team:NJU China/Project

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Overview Chassis Targeting device Killing device Application

Overview

Targeting medication 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.

Using the principles of synthetic biology, we aimed at building up a new drug delivery system named Bio-missile. We wanted to encapsulate highly specific molecular medicine siRNA into targeting exosome for site-specific delivery.

Exosomes are lipid bilayer vesicles, which are naturally secreted by almost all cell types, playing crucial roles in intercellular transport of bioactive molecules. Given their role as natural transporter, exosomes potentially represent a novel and exciting drug carrier for therapeutic purpose. Thus, modification of exosomes derived from cells may realize the goal of delivering drugs to local cellular environment.

Outside modification:
To endow the exosome with site-specific recognition ability, we designed a fusion proteins comprising of exosome surface protein lamp 2b, and receptor-binding peptides. The lamp 2b can bring the receptor-binding parts of the fusion protein onto the surface of the exosome. Thus the modified exosome will, in theory, has the ability to target specific tissues and organs.

Nside modification:
We have managed to encapsulate our ‘kill device’ siRNA into our exosomes. Recently, small interfering RNA (siRNA) is emerging as a promising therapeutic drug against a wide array of diseases and it functions to destroy viral gene through the RNA interference pathway. By designing siRNA against certain viral genes, we can use siRNA as molecular medicine for disease treatment.

By transfecting our chassis, HEK 293T cells, with siRNA plasmids and collecting exosomes, we filled the exosomes with therapeutic siRNAs. And via the engineering of the target protein, we also endowed the exosome 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, causing targeted destruction of diseases. Our project will open up avenues for therapeutic applications of exosomes as biomissile.

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