Design of Multi-Functional SplitCore HBV Capsids for Precisely Controlled Multi-siRNA Delivery in Cancer Therapeutics

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Nontechnical descriptionBy 2030, there could be 27 million incident cases of cancer worldwide. Gene silencing therapies offer unique promise for cancer treatment by providing highly potent and target-specific silencing of genes during cancer progression. The major technological hurdles confronting the use of gene silencing for cancer treatment are the needs for improved delivery and protection from rapidly degradation under physiological conditions. To tackle this problem, this program will design multi-functional Hepatitis B Virus (HBV) capsids suitable for cell-specific delivery by targeting receptors that are highly expressed on the surface of tumors. HBV capsids are designed to release the gene silencing agents inside of cells based on pH changes. The students trained on this project will be exposed to multi-disciplinary training in the context of research that is anticipated to significantly advance biomaterials capabilities. Technical descriptionThe development of effective therapeutic vehicles for siRNA delivery is of essential importance in cancer treatment. Virus-like-particles (VLPs) based on the SplitCore HBV technology are ideally suited for this purpose by providing a transformative approach to attach four unique decorations (3 exterior, 1 interior) to each HBV monomer into a highly modular nanoplatform suitable for customizable cell targeting and siRNA capture/release. This significant advance can enable key increases in both cell specificity and therapeutic efficacy through incorporation of well-defined combinations of targeting ligands as well as siRNAs, ultimately creating hybrid structures that fuse the delivery efficiency of viruses to the design versatility of non-viral vehicles. The simplicity of the design allows the creation of highly adaptable, multi-functional HBV capsids suitable for a range of cancer targets.