Surface-Associated Delivery of Genes and Oligonucleotides in vivo (20071(v))

This invention describes a novel system for the controlled, efficient delivery of DNA or oligonucleotide (ON) complexes from a supporting scaffold that could be used in tissue engineering or regeneration and gene therapy. Using the proposed methods, a scaffold made of a biocompatible polymer would be implanted. Cells from the surrounding tissue would migrate across the scaffold, internalizing the gene or ON into the cells of the tissue. Multiple genes could be placed on the scaffold material to direct cellular responses. In this novel method, non-covalent bonds are formed between the nucleic acid and accessory molecules (e.g., cationic peptides). A fraction of these accessory molecules contain functional sites that allow the DNA complex to be tethered to a solid support. The support can be any substrate that supports cell adhesion, such as natural extracellular matrix (e.g., collagen), or a biocompatible polymer.

Tethering of the complex localizes the DNA or ON to the 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. 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.

An advantage of this system is that it provides the potential for spatial and temporal control of gene delivery. The location of the DNA on the solid surface can be regulated, providing spatial control of gene delivery. Temporal control is obtained by regulating uptake of the complex by the cell, which may be obtained through the design of the tether and its degradation rate. The surface density of the nucleic acid, number and type of tethers, properties of the scaffold, and design of the accessory molecules are major design variables that tailor the release and uptake of nucleic acids.

SUMMARY: A primary goal in the field of gene therapy application is the development of a method for safe, controlled, and efficient delivery of genes in vivo. The limitations of current approaches create soluble DNA condensates that do not transfect cells with high efficiency because of their clearance from tissue. In addition, these approaches do not allow for much spatial or temporal control over gene delivery. This invention provides a novel system of controlled gene and ON delivery with enhanced transfection by providing high concentrations in the cell microenvironment. Additionally, the system can be used to create patterns of gene expression within a cell population.

A patent application has been filed and Northwestern is interested in licensing this technology.

Type of Offer: Licensing

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