Roche licenses zinc finger tech to aid its discovery programmes

The deal includes the non-exclusive worldwide rights for the commercial use of ZFN-generated transgenic animals in the production of therapeutic and diagnostic products as well as a research agreement that will see all three firms collaborating to develop new cell lines and transgenic animals using the technology.

The transgenic animals and cell lines will be used as disease models in Roche's discovery programmes as well as potentially being used to generate vaccines and therapeutic biological drugs.

ZFNs are modified zinc finger proteins (ZFPs) that can be used to modify target genes in a variety of organisms.

"There is growing appreciation of the value of ZFN technology as a rapid, reliable and highly specific tool for modifying genes in eukaryotic cells and whole organisms," said Dr David Smoller, president of Sigma-Aldrich's Research Biotech Business Unit.

"We are excited to be working with Sangamo to provide Roche with high-value ZFN reagents for the generation of transgenic animals.

ZFN technology promises to enable the generation of a variety of transgenic models of human disease, expediting drug development and production."

Last year, [http://www.labtechnologist.com/news/ng.asp?id=78091] Sigma-Aldrich licensed the technology for use as research reagents in a deal that could be worth up to $35m (€22m).

ZFPs are naturally occurring transcription factors that bind to DNA to regulate gene expression and occur in a range of organisms from yeast to humans.

They can be engineered to target specific gene sequences as well as to incorporate a nuclease component and form ZFNs that can modify the target gene.

This modification can lead to the target gene being eliminated or 'knocked out' of a species which can then be used to generate in vivo disease models.

A recent study published in Nature Biotechnology showed that ZFNs could be used to generate zebrafish disease models in which the ZFN-targeted gene was eliminated.

"Using ZFNs in zebrafish, a widely recognized system for human disease modeling and in vivo drug discovery, resulted in the generation of fish in which the ZFN-targeted gene has been eliminated or 'knocked out'," said Dr Philip Gregory.

"Apart from the mouse, the majority of other animals including zebrafish have historically lacked methods for precision targeted mutagenesis.

This publication demonstrates that ZFNs present a powerful solution to this problem with application across virtually any species for any gene."

In an article in the following issue of Nature Biotechnology , Sangamo's ZFN technology was shown to induce HIV-1 resistance in human immune CD4 T-cells by modifying the CCR5 gene which plays a key role in HIV T cell attachment and penetration.

"We have demonstrated that a single treatment with our CCR5-specific ZFNs generates a population of HIV-resistant human T-cells similar to the situation in individuals carrying the natural CCR5-delta32 mutation," said Dr Dale Ando, Sangamo's vice president of therapeutic development.

"ZFN-modification of these cells is permanent and makes them resistant to HIV.

The modified cells preferentially survive and expand in an animal after HIV infection, providing a reservoir of healthy and uninfectable immune cells.

In an HIV-infected patient, such modified cells could be available as a protected reservoir within the immune system to fight both opportunistic infections and HIV itself."

The firm expects to initiate clinical trials to evaluate the approach by the end of the year.