An Improved Non Viral System for Tumor Specific Suicide Gene Therapy
Description of Invention:
Numerous tumor specific promoters have been identified and developed for targeted gene therapy. Survivin promoter activity is upregulated in 75% of tumors, however the activity is specific but low, resulting in sub-optimal suicide gene expression. Combination of survivin promoter with Bax, a proapoptotic gene, previously used in such therapy has demonstrated low efficacy.
Scientists at NCI have made a plasmid construct consisting of survivin promoter driven mutant form of bax that is constitutively active. This construct is more potent than the wild type bax, improving its efficacy several-fold, while, retaining specificity for tumors, as determined by in vitro and in vivo studies.
This new technology does not use CMV or SV-40 promoters, alleviating the need for modifications for commercialization.
Advantages:
Can be used with cationic liposomes or other DNA delivery systems.
Can be incorporated into adenoviral and lentiviral vectors.
Excludes viral promoters.
Can be modified easily to use other promoters/suicide genes.
Applications:
Cancer therapeutics
Targeted Gene therapy
Market:
In patients with advanced solid tumors or recurrences despite surgery, chemotherapy can provide quality survival. However, responses are usually partial, often disappointingly brief and unpredictable and coupled with side effects. These limitations of traditional cytotoxic chemotherapy make it necessary to explore other therapies such as targeted gene therapy. Viruses, while the carrier of choice in most gene therapy studies, present a variety of potential problems to the patient -- toxicity, immune and inflammatory responses, and gene control and targeting issues. In addition, there is a fear that the viral vector may recover its ability to cause disease in the patient. Our new technology addresses some of the above issues making it a suitable agent for cancer and gene therapy.
Patent Status:
DHHS Reference No. E-245-2007/0 -- Research Tool Patent protection is not being sought for this technology.
Licensing Status: Available for non-exclusive licensing.
Collaborative Research Opportunity:
The National Cancer Institute Center for Cancer Research Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize tumor specific suicide gene therapy using survivin promoter driven mutant bax. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.
Portfolios: Cancer
Cancer -Therapeutics-Immunoconjugates Cancer -Therapeutics
For Additional Information Please Contact: Sabarni K. Chatterjee Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: 301/435-5587
Email: chatterjeesa@mail.nih.gov
Fax: 301/402-0220
