Surface-Associated Delivery of Genes and Oligonucleotides for High Throughput Functionality Analysis (20071ht)
Investigators at Northwestern University have invented a novel system appropriate for the high-throughput analysis of gene function and an approach for the controlled, efficient delivery of DNA or oligonucleotide (ON) complexes from a surface, from which multiple genes or ONs can be delivered in parallel. In this approach, non-covalent bonds are formed between the nucleic acid and accessory molecules. Some of these accessory molecules are then tethered covalently to a solid support, which can be patterned to allow for different domains with each containing a different nucleic acid. The support can be any substrate that supports cell adhesion, such as glass.
Tethering of the complex localizes the DNA or ON to the solid surface, placing the nucleotide directly in the cell microenvironment. Though the complex is localized to the solid substrate, the nucleotides remain available for uptake into cells. The transfection is localized to the site at which the DNA is tethered. Since only a portion of the accessory molecules are covalently tethered to the substrate, the DNA or ON can be internalized directly from the surface. Alternatively, the tethers linking the substrate to the surface could be broken, releasing the entire complex as a soluble factor in the immediate cellular domain. The surface density of the nucleic acid, properties of the scaffold, and design of the accessory molecules are major design variables that tailor the release and uptake of nucleic acids.
APPLICATION and SIGNIFICANCE: The system has potential applications in the field of high throughput analysis of gene function. This procedure would be similar to microarray technology methods, which quantitatively compare the expression level of thousands of genes under controlled conditions. With this method, hundreds of genes or ON would be patterned on the solid surface, and a cell population would be seeded across the substrate. In particular, antisense ON could be used to inhibit protein expression, or wild-type or mutated cDNAs could be attached to the substrate to over-express wild-type or aberrant forms of a protein of interest. The responses of the cells transfected with the DNAs (sense or antisense ON, wild-type or mutant cDNAs) to various pharmacological stimuli could then be measured and evaluated.
SUMMARY: To date, a major barrier in the in the realm of gene delivery is that few efficient, controlled methods exist for the delivery of DNA or ON complexes. This invention provides a novel system of gene and ON delivery that allows for high throughput of transfection of hundreds of gene products in an efficient and timely manner. Furthermore, this technology allows an examination of the relationship between gene expression and changes in protein function.
U. S. Patent No. 6,890,556 has issued and Northwestern is interested in licensing this technology.
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