An Improved Non-Viral Gene Therapy System

Background:
The National Cancer Institute's Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a tumor-specific gene therapy agent. The technology is also available for non-exclusive licensing.

The limitations of anti-cancer chemotherapy have made it necessary to explore other treatment options such as targeted gene therapy. Although viruses are the carrier of choice in most gene therapy studies, their use presents a variety of potential problems to the patient, including toxicity, immune and inflammatory responses, and the potential that the viral vector will recover its ability to cause disease in the patient. New technology developed at NCI addresses some of these issues, making it a suitable agent for cancer and gene therapy.

Technology:
Numerous tumor specific promoters have been identified and developed for targeted gene therapy. Survivin is a member of the IAP (inhibitor of apoptosis) gene family. Although survivin promoter activity is upregulated in 75% of tumors with a high degree of specificity, the activity is low, resulting in sub-optimal suicide gene expression. Combination of survivin promoter with bax (Bcl-2-associated X protein), a proapoptotic gene, has also demonstrated low efficacy when used in gene therapy.

Scientists at NCI have made a plasmid construct consisting of survivin promoter driven mutant form of bax that is constitutively active. Both in vitro and in vivo studies have demonstrated that this construct is more potent than the wild type bax, improving its efficacy several-fold, while, retaining specificity for tumors.

Further R&D Needed:

• Testing constructs in murine models of cancer to determine both efficacy and safety.
• Determine the best method of delivery of the plasmid in vivo using both xenograft and syngenic murine cancer models.

R&D Status: in vitro and in vivo validation

IP Status:
Because this technology is a research tool, patent protection is not being sought pursuant to NIH Patent Policy.

Value Proposition--Solution:

• This new technology does not use viral promoters, alleviating the need for modifications for commercialization Ability to improve bax potency while retaining tumor specificity
• Reduction of complications associated with viral gene therapy carriers.
• Easy modification for use with other promoters/suicide genes.
• Potential use with cationic liposomes or other DNA delivery systems.
• Ability to incorporate viral construct into adenoviral and lentiviral vectors

Contact Information:
John D. Hewes, Ph.D., NCI Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov

Reference:  #634 JH

Posted 03/03/2007