IMPROVED GENE TRANSFER AND WOUND HEALING

Impaired wound healing is a major complication of diabetes, a disease that affects up to 16 million Americans. More than 67,000 patients with diabetes require foot amputations each year in the U.S. alone. Neovascularization (angiogenesis) and extracellular matrix deposition (collagen synthesis), central to the normal wound healing process, are impaired in diabetics. Although the underlying causes of impaired wound healing in diabetics are not understood, it has been observed that the expression of several genes encoding potential angiogenic mediators is reduced in the wounds of diabetic animals.

Investigators at UCSF have discovered that some members of the Homeobox (Hox) transcription factor family may have significant potential for improving the healing of diabetic ulcers. In wounds that heal normally, expression of HoxD3 gene is significantly upregulated in the endothelial cells (critical for angiogenesis and wound healing) adjacent to the wound site. In contrast, our investigators have observed that expression of this gene is delayed and significantly reduced during wound healing in diabetic animals. Experimental evidence indicates that HoxD3 may also regulate collagen synthesis.

Our investigators have also devised a simple topical method (using methylcellulose) for delivering these genes or proteins to a wound. In diabetic animals, a single application of this gene to an open wound causes significantly faster wound closure and increased production of type I collagen, resulting in overall improved wound healing. Recent findings indicate that another member of the Hox family is even more potent than HoxD3 in terms of accelerating wound closure. Features of this novel treatment for diabetic wounds are:

• Single easy topical application
• Stable formulation
• Inexpensive to manufacture

This intellectual property portfolio from UCSF would thus provide a company with a proprietary position for developing novel methods and compositions for improving wound healing under conditions of impaired healing capabilities, such as diabetes.

Intellectual Property: UCSF has filed U.S. patent applications covering methods and compositions useful in localized transfer of genetic material or proteins (Application #20030109450 and #20040228920).

References:
- Uyeno LA, Newman-Keagle JA, Cheung I, Hunt TK, Young DM, Boudreau N. HoxD3 expression in normal and impaired wound healing. J. Surg. Res. 2001 Sep; 100(1): 46-56.
- Mace KA, Hansen SL, Myers C, Young DM, Boudreau N. HoxA3 induces cell migration in endothelial and epithelial cells promoting angiogenesis and wound repair. J. Cell Sciences 2005; 118: 2567-2577.

If you would like to receive further information about this technology and potential licensing opportunities, please contact:

Sunita Rajdev, Ph.D.
Licensing Officer
(415) 353-4470 phone
(415) 348-1579 fax
Sunita Rajdev

Reference: OTM Case #SF01-078