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Novel Nanostructured Surfaces for Substrate-Mediated Gene Delivery

Albert Nguyen and Freshta Baher; collaborator: Mathias Schubert/cnfm

Novel Nanostructured Surfaces

In order to overcome barriers known to hinder DNA delivery efficiency, there is a need to develop new delivery methods capable of localized delivery of DNA and other biomolecules such as proteins and therapeutic compounds. Substrate-mediated gene delivery (SMD) describes the delivery of plasmid DNA or DNA complexed with nonviral vectors to cells from a surface, with the DNA immobilized to a biomaterial or substrate through specific or nonspecific interactions.

Immobilized DNA is targeted to cells adhered to the substrate and its local concentration is increased in the cell microenvironment, which has been shown to enhance transfection and allow for patterned delivery. However, for SMD on traditional two-dimensional surfaces, the amount of DNA that can be loaded is limited by surface area constraints and direct contact between immobilized complexes and cells could induce vector toxicity. Therefore, we propose to design new substrates for SMD, which immobilize DNA within the voids of nanostructured columnar thin film surfaces to provide greater surface area for increased DNA loading and to shield cells from direct contact with DNA vectors by loading the DNA in the columnar void spaces beneath adhered cells.