Open Competition 1 - Biotechnology

Immune System Evading Targeted Gene Therapy Vectors

Sponsor: ISOGENIS, Inc.

• Project Performance Period: 6/1/2003 - 5/31/2006
• Total project (est.): $2,154,983.00
• Requested ATP funds: $1,998,903.00

Numerous diseases, such as cystic fibrosis, are caused by genetic mutations that lead to deficient functioning of the affected tissues. Gene therapy aims to cure these diseases by introducing or repairing a crucial gene. However, a serious obstacle to successful gene therapy is the patient's immune system, which typically attempts to suppress the expression of the therapeutic gene and its product. Isogenis, in a previously funded ATP project, is developing a proprietary "engineered veto" technology to prevent the rejection of transplants. In the course of that project, the company produced preliminary evidence for elimination of immune responses elicited by gene therapy. Isogenis now plans a three-year project to develop and test novel gene therapy vectors, such as engineered viruses, that can treat genetic diseases while evading immune responses. These vectors are meant to accomplish two important objectives: to eliminate only the specific immune responses launched against vector components and the therapeutic gene itself, and to deliver the therapeutic gene to only the targeted tissue. The company plans to design a gene therapy vector for treating cystic fibrosis that best meets these two objectives and then evaluate it in culture and in an animal model. Cystic fibrosis, an inherited condition characterized by recurring lung infections, has been chosen as the first therapy target because it is common, has been extensively studied, has been replicated in a well-characterized mouse model, and cannot be cured by any means other than gene therapy. The ATP funding could accelerate development of the new technology by five years and advance the research beyond the proof-of-principle stage so that Isogenis can attract private funding and strategic partners. If successful, the project would provide a basis for clinical trials. The research could lead to a cure for cystic fibrosis, thereby doubling life expectancy for patients and cutting treatment costs (now $58,000 annually for each patient) dramatically. Furthermore, minor modifications to the new technology's modular design could produce therapeutic agents for a wide variety of genetic and autoimmune diseases, including rare ones.

For project information:

John R. Price, (303) 886-0700
jprice@isogenis.com

ATP Project Manager

Mrunal Chapekar, (301) 975-6846
mrunal.chapekar@nist.gov