Enzyme-Mediated Construction of miRNA Hairpin SNA's for in vivo Applications

Project: Research project

Project Details

Description

When cellular RNA levels change drastically, unwanted cellular pathways can become activated, including cancer. The central goal of this research is to design a nanoscale genetically tunable therapy capable of correcting dysregulated RNA expression levels inside a cell. Using nanotechnology, the deployment of RNA within cells has been achieved. Although promising, research to date has mainly focused on the delivery of short RNA (<25 bases). It is well known that structure is a key component of RNA function. Therefore the delivery of larger, more highly structured
molecules such as aptamers and pre-microRNA (80-120 bases) will help expand the breadth of RNA therapies that can be developed for treating diseases such as cancer. The miRNA hairpin (HP) mir211 has been chosen for this project as it has been shown to be implicated in many forms of cancer, including melanoma.1 Delivery of mir211 into cells has only been possible with the use of toxic transfection agents, therefore limiting its study to that of in vitro analysis. This research plan outlines a strategy for designing a mir211-conjugated spherical nucleic acid (SNA) on a gold nanoparticle (NP) surface. The assembly will be mediated by an enzymatic ligation - a novel approach in RNA attachment strategies on colloidal nanoscale surfaces. This strategy has the potential to improve the coverage and assembly of miRNAs at a NP surface, and, upon successful
delivery, improve the likelihood of therapeutic genetic effects within cells.
StatusFinished
Effective start/end date2/1/147/17/15

Funding

  • Pharmaceutical Research and Manufacturers of America Foundation, Inc. (Letter 3/6/14)

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