Control Of Gene Expression Using A Heat Shock Protein Promoter In Combination With Local Heat

Text of Federal Register notice forwarded for publication by NIH on December 20, 1996
National Institutes of Health

National Center for Research Resources: Licensing Opportunity and/or Opportunity for a Cooperative Research and Development Agreement (CRADA) for the development of technologies and applications for spatial and temporal control of gene expression using a heat shock protein promoter in combination with local heat

AGENCY: National Institutes of Health, PHS, DHHS

ACTION: Notice

SUMMARY: The National Center for Research Resources (NCRR) and collaborating institutes of the NIH are seeking CRADA partners and/or licensees for the development of different technologies and applications to provide a safe and efficient introduction of exogenous genes under the control of a heat-sensitive promoter and to assess the efficacy of spatial and temporal control of gene expression using MRI guided FUS. This project is with the In Vivo NMR Research Center, NCRR, in a collaborative study with the National Institute on Aging, the National Heart Lung and Blood Institute, and the National Institute of Dental Research of the National Institutes of Health, Bethesda, Maryland.

The NCRR has applied for patents claiming this core technology. Non-exclusive and/or exclusive licenses for these patents covering core aspects of this project are available (in accordance with 35 U.S.C. 207 and 37 CFR Part 404) to interested parties.

DATE: There is no deadline by which license applications or CRADA proposals must be received.

ADDRESSES: CRADA capability statements/proposals and questions about this opportunity should be addressed to Mr. Tom Ingalls, Technology Transfer Specialist, NCRR, Bldg. 12A/Room 4057, Bethesda, Maryland 20892-2490; Phone: 301/496-6235.
Licensing applications and licensing inquiries regarding this technology should be addressed to Mr. Larry Tiffany, Office of Technology Transfer, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; Phone: 301/496-7735, ext. 206; Fax: 301/402-0220.
Information on the patent and patent applications and pertinent information not yet publicly described can be obtained under a Confidential Disclosure Agreement. Respondees interested in licensing the invention(s) will be required to submit an Application for License to Public Health Service Inventions. Respondees interested in submitting a CRADA proposal should be aware that it may be necessary to secure a license to the above patent rights in order to commercialize products arising from a CRADA agreement.

SUPPLEMENTARY INFORMATION: In many instances, it is desirable to express exogenous genes only in certain tissues, and/or at will at certain times, and/or only to a certain degree. However, current gene transfer and exogenous gene expression protocols do not provide adequate means of simultaneously controlling which cells in a heterogeneous population are transformed and when, where, and to what degree the transferred genes are expressed. Here, we seek to accomplish the spatial and local control of expression of exogenous genes using a heat-inducible promoter (such as the inducible hsp70 promoter) in combination with local heat, preferably provided by Magnetic Resonance Imaging (MRI) guided Focused Ultrasound (FUS).

The goals of this project are to use the respective strengths of both parties to achieve one or more of the following:
1. Evaluate the feasibility and safety of gene therapy utilizing a range of suitable vectors as a treatment approach to carry out a systemic gene transfer in which the therapeutic gene is under the control of a heat-sensitive promoter showing negligible constitutive expression at normal body temperature.
2. Evaluate the feasibility of controlling the local and temporal induction of gene expression (pharmacokinetics) using local heat provided by Magnetic Resonance Imaging guided Focused Ultrasound.
3. Develop and evaluate gene therapy products for use in experimental animal models and for human use based on the above control of expression.

It is anticipated that the commercial collaborator(s) will participate in ongoing studies on one or more of the research projects involving:
1. The transfer of genes for various lymphokines into experimental animal models based on an adenovirus vector or other vectors. It is highly desirable that the collaborator have the resources to provide new effective vectors for gene transfer.
2. The modulation of the inducibility of the heat-sensitive promoter using appropriate modifications of the promoter and by using antiinflammatory or other drugs.
3. Dosage and toxicity of local production of lymphokines applied to cancer and other diseases.
4. Initial applications in the field of anticancer therapy, immunomodulatory gene products and angiogenesis.

The collaborator may also be expected to contribute financial support under this CRADA for supplies and personnel to support these projects.