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
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