MONTREAL - An HIV protein that prevents infected cells from proliferating is the subject of a strategic alliance between Montreal-based Theratechnologies Inc. and Cambridge, Mass.-based Genetix Pharmaceuticals Inc.

During the replication of the HIV virus, the Vpr protein, identified in 1988 by Theratechnologies' Eric Cohen, is specifically incorporated into the newly produced virus, making it an ideal target for gene therapy.

Genetix has licensed the exclusive rights to the Vpr gene from Theratechnologies for use in its lentivral packaging cell line, LentiPak, its second-generation gene delivery system that has the ability to integrate therapeutic genes into the chromosomes of non-dividing cells in both in vivo and ex vivo settings.

Andre de Villers, president and CEO of Theratechnologies, said the fact that Vpr protein plays an important role in the viral replication of HIV has attracted a great deal of attention. This alliance with Genetix is the second to be based on the company's Vpr technology.

In collaboration with Chiron Corp., of Emeryville, Calif., “we have research aimed at combining both companies' technologies, Chiron's HIV-specific single-chain intracellular antibodies and our modified Vpr protein, to counter HIV replication,“ de Villers said.

Theratechnologies discovered the site of interaction between the Vpr protein and that of another protein precursor, Gag, which is essential to the formation of HIV. A chimeric Vpr protein was then produced which, when incorporated instead of the natural viral protein, affects the virus morphology and has a significant impact on its replication.

Studies suggest that Vpr stops cells from replicating by blocking the process of cell division at an early stage.

Ronald Dorazio, vice president of business development at Genetix Pharmaceuticals, told BioWorld International the Vpr protein prevents cells from proliferating, making it ideal for use with the LentiPak system.

Genetix will be using the Vpr gene with LentiPak to virtually eliminate the safety concerns generated during the manufacturing process of gene therapies. In particular, the technology will be applied to its ongoing cancer and cardiovascular gene therapy programs.

Genetix's research effort is concentrated on improved gene transfer systems. Current projects are aimed at efficient and permanent transduction of non-dividing cells both in vivo and ex vivo. Methods to target particular cell types and organs in vivo also are being explored. These efforts all will build upon a retrovirus' unique ability to permanently integrate its genes in a patient's chromosomes.

Retroviral vectors are the most common gene delivery systems used in clinical trials, due, in part, to their unique ability to integrate genes into chromosomes, permitting a long-term therapeutic effect. However, lentiviral vectors have the added features of being able to deliver therapeutic genes into non-dividing cells, as well as to be used directly in vivo.

This creates opportunities to perform long-term gene therapy in such clinically important tissues as brain, liver, bone marrow, and skeletal and cardiac muscle.

Deal Boosts AIDS Research

The alliance not only gives Theratechnologies the opportunity to position itself in a very promising niche of gene transfer or gene delivery, but offers the company significant advantages, said de Villers.

From a strategic point of view, this partnership enables Theratechnologies to consolidate its position in the field of AIDS, since it will acquire back from Genetix the world license for its gene transfer system for AIDS-Vpr gene therapy applications.

This alliance eventually could generate a significant stream of revenues for Theratechnologies, because of the numerous applications derived from therapeutic gene transfer, namely in the treatment of cancer and cardiovascular disease. Genetix has agreed to pay Theratechnologies up-front, milestone and royalty payments stemming from any sublicenses that may be granted or from the sale of any therapeutic product incorporating its Vpr technology. *

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