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Nanomaterials for Gene Knock-down

Hill Laboratory

Nanomaterials have the capacity to bind multiple biomolecules. They also have intrinsic signaling functions that can be used for targeted delivery of biomolecules to specific cells and tissues. In this project, we will utilize our established interdisciplinary links across molecular physiology, surface chemistry, and nanomaterials development to provide a platform enabling the discovery of new biomolecular-nanomaterial interactions.

Current technologies for the study of gene knock-down utilize interfering RNAs that are delivered into the cells in vitro, either by transfection using viral vectors, or by using a severe chemical treatment to allow the active molecules to pass through the plasma membrane. These approaches are not always effective, and have limited use in understanding physiology. Nanomaterials have been shown to provide an effective delivery platform for gene knock-down strategies. In this approach, specific RNA or RNA mimics, when bound to nanostructures, can be introduced to the cellular cytoplasm. Using a nanostructure delivery package enables the dose of the gene knock-down agents to be controlled and increases the time that the gene knock-down remains active. In this project we will build upon our current interdisciplinary links to address four specific aims:

Aim 1: Develop a nanostructure platform to deliver bioactive molecules in vitro.
Aim 2: To demonstrate gene knock-down by introduced nanostructures.
Aim 3: Targeted delivery of nano-based gene knock-down to specific cell types.
Aim 4: Development of generic applications for bio-nanostructures.

Our approach in developing nanostructures for delivery of RNA molecules has enormous power for development of more generic technologies. Our studies, understanding, and manipulating the covalent linkage of RNA to nanostructures provides the basis for binding a wide array of nucleic acids and their use in understanding physiology.