Cell Regulation with Polyvalent Nanoparticles
ABSTRACT: Polyvalent nanoparticle constructs have unique properties that make them ideal for gene regulation applications, while overcoming many of the challenges which have prevented oligonucleotides from being developed into viable therapies. Specifically, AuraSense is developing constructs which are highly resistant to nuclease digestion, have high binding constants for intracellular targets, and, uniquely, have exhibited high entry into every cell type tested to date (over 50 cell types including primary cells, tissues and neurons). The AuraSense constructs thus represent a significant advance in gene pathway regulation technology while displaying the characteristics of an ideal gene therapy system. Building on our initial success, we are proposing to develop optimal constructs for application in the control of gene and protein expression. Objective 1 experiments will be designed to demonstrate and optimize: 1) Ability to deliver conjugate nanostructures into both prokaryotic and eukaryotic cells, 2) Ability to deliver oligonucleotides including siRNA, DNA and modified nucleic acid structures, and 3) Qualitative and quantitative assessment of cellular entry. Objective 2 will determine the 1) Functional gene regulatory effect in prokaryotic and eukaryotic cells, 2) Biological compatibility and toxicity, and 3) Comparison with commercially available lipid and polymer systems (e.g. Lipofectin and Cytofectin). BENEFIT: AuraSense"s nanoparticle constructs have great potential as broadly effective, non-toxic agents for cellular transfection of genetic material. AuraSense nanoparticle technology has been developed in numerous proof-of-concept applications and has been the subject of consistent commercial interest to date. This platform stands to significantly advance transfection as a tool for life science researchers and for increasing the safety of troops in the field. AuraSense"s nanoparticle platforms are highly relevant to two markets: Chemical Transfection (as used for research applications) and Biodefense.
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