Nanoscale Architectures for Controlled Gene Expression

Ut-Battelle, Llc-Oak Ridge National Lab, Oak Ridge TN

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Abstract

DESCRIPTION (provided by applicant): The merging of recent advances in the synthesis of nanostructured materials with the mature technology of microfabrication is beginning to provide complex devices capable of interfacing with biological systems at the molecular scale. The goal is to develop and implement such multiscale devices for the direct manipulation of transcriptional processes - whereby individual (or groups of) genes within a single (or group of) cell(s) may be induced or repressed via electronic control. The approach is to exploit nanoscale features of these devices as an interface to cell(s), whereby tethered genetic material may be introduced into a cell and regulated by external stimuli applied through the platform of the multiscale device. Arrays of vertically aligned carbon nanofibers (VACNFs) provide a unique opportunity for realizing these goals. VACNFs are high aspect ratio structures that feature nanoscale tip diameters and micron lengths and that may be synthesized in a vertical orientation at desired locations upon planar substrates. VACNFs may be interfaced directly to cellular matrices, and their nuclei, and used for the massively parallel introduction of DMA, which can be tethered and expressed from the nanofiber scaffold in many cells. Further, nanofibers may be fabricated with individual electrical connectivity, thereby providing nanoscale electrochemically active structures that can be spatially and temporally addressed. This combination of properties provides a novel vehicle for the introduction of genes and the electronic control of their expression in cell and tissue matrices. This will be approached through the following aims. Aim 1. Developing a Fundamental Understanding of Nanofiber/Cell Interaction Aim 2. Development of Methods to Reduce Lateral Transfer of Tethered Template Aim 3: Development of Electronic Techniques for Modulating Transcription of Nanofiber-Tethered Plasmid DNA Including shRNA Expression Vectors.