The new technology developed during Phase I offers a novel approach to treating ischemia effectively and safely. We developed muscle-specific promoters that provide higher levels of expression than natural promoters and altered regulatory properties.
The aim of the Phase II research is to apply these advances to develop non-viral gene medicines that will stimulate angiogenesis and provide a safe and effective therapy for ischemia. GENEMEDICINE has developed a novel approach using polymeric formulations to enhance gene delivery. We have shown in rats that IM injection of muscle-specific GH gene medicine formulated in PVP resulted in levels 10-15-fold higher than the plasmid in saline. This proposal describes the development of a muscle-specific plasmid that expresses hVEGF. The hVEGF expression plasmid will be optimized for high level, tissue-restricted expression by including a synthetic muscle-specific promoter and a hVEGF coding sequence that contains optimized human codons. The muscle-specific gene medicine will consist of the muscle- specific, codon optimized hVEGF expression plasmid complexed with the polymeric gene delivery system. As such, it has significant advantages over the CMV-based plasmids delivered in saline developed by others. The gene medicine will be tested in the rabbit ischemia model and the preclinical studies completed for clinical trials.

Proposed Commercial Applications

Currently, the prognosis for patients with chronic critical leg ischemia is grim. Approximately 150,000 people per, year have been reported to have ischemia severe enough to require lower limb amputation because they are unresponsive to conventional medical or surgical treatment. Following amputation, the mortality rate is high. There is a compelling need for effective treatment strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44DK048567-02
Application #
2715211
Study Section
Special Emphasis Panel (ZRG2-GNM (02))
Program Officer
Mckeon, Catherine T
Project Start
1994-09-20
Project End
2000-08-31
Budget Start
1998-09-24
Budget End
1999-08-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Valentis, Inc.
Department
Type
DUNS #
City
Burlingame
State
CA
Country
United States
Zip Code
94010