Ankit Agarwal |
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Degree: PhD Department: Material Chemistry and Biomolecular Materials College: Sweeney Hall Contact: Email, Homepage These self-assembling copolymers are positively charged at physiological pH and are protonated at low pH, giving them good DNA complexation and endosomal disruption capabilities. Aqueous solutions of these copolymers exhibit temperature and pH dependent gel-sol transition. The polymer can be loaded with DNA in an aqueous phase at low temperatures (below 4 °C) where it exists as sol. In this form polymer is injectable. On subcutaneous injection and subsequent heating to body temperature, the loaded copolymer forms a gel that can act as a sustained-release matrix for polymer-DNA complexes over a period of time. The detailed morphology of the polyplexes is studied using Cryo-TEM and multi-angle light scattering (MALS). LDH assay is applied to find the cytotoxicity of the polymers and polyplexes. In-vitro studies have been done on several mammalian cancer cell lines to study the transfection efficiency of the polymers using luciferase and Green Fluorescence Protein as reporter genes. Herpes simplex virus thymidine kinase (HSV-TK) (in combination with the prodrug Ganciclovir) will be used as the therapeutic suicide gene. For cell-specific gene delivery EGF (Epidermal Growth Factor) will be added as ligand to the polymer. In-vivo studies on mice will be performed soon. |
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