SAGEspeed to create genetically engineered rodent research models in months

Sigma-Aldrich has launched SAGEspeed, a programme to develop human disease models in rodents using its proprietary novel CompoZr Zinc Finger Nuclease (ZFN) gene editing technology.

The programme will give researchers access to custom creation services for developing genetically-engineered 'knockout' rodent animal models for use in research and the development of therapeutic treatments in as little as four to five months, which is about a third of the time it would take using an embryo stem cell approach.

The technology and methodology employed by SAGEspeed not only reduces by around two-thirds the cycle time needed to create knockout mouse models using conventional embryo stem cell-based technologies, it can also create targeted knockout rats.

"The advantage is twofold," said Gilles Cottier, president of SAFC (Sigma-Aldrich Fine Chemicals). "First is that rat is a much better model in which to study a disease than mice because it is closer to the human genome; and second, nobody has been able to do that before."

Zinc Finger Nuclease technology was licensed by Sigma-Aldrich from California-based Sangamo Biosciences in July 2007 for use in r&d applications. The two companies entered into a collaboration to develop and commercialise research reagents for targeted genome editing utilising ZFN technology.

CompoZr ZFN was launched in September 2008 and used to develop novel genetically modified animal models of human disease. The first of these, which was announced in October 2009, was the "knockout" rat model for the development of transformative treatments for Parkinson's disease, in conjunction with the Michael J. Fox Foundation.

The SAGEspeed programme will be available through Sigma Advanced Genetic Engineering (SAGE) Labs, which will offer customers dedicated model design support, significantly reduced model development time and comprehensive management of the entire project from initial consultation through the delivery of the custom rodent models.

"The researcher simply provides his gene target and we will do the rest," explained Dr Edward Weinstein, director of SAGE Labs. "Once the customer's requirements have been discussed, the Knockout rodent model is developed to detailed specifications. All animals are produced and carefully fostered into maturity at our specific pathogen-free, bio-secure facility."

In a further development in mid-October 2009, Sigma-Aldrich acquired from Sangamo Bioscience the exclusive rights to use ZFN technology in bioproduction. This will enable SAFC to link its expertise in cell culture with functional genomics to generate novel enhanced cell lines for bio-manufacturing and give the company the freedom to work with clients to create custom manufacturing processes that utilise enhanced cell lines and custom media.

These rights mean that SAFC is able to enter into conversations with large pharma companies to sublicense the technology for use in their pipeline in preclinical or Phase I or II to develop models for certain drug targets and even - further down the road - in commercial manufacturing, Cottier said.

Sigma-Aldrich has now launched the SAGE Priority Partners Program, through which it plans to build a network of researchers to evaluate the 'knockout' rat models across a number of fields, including neurobiology, toxicology, cardiology and immunology.

Partners will be asked to conduct their own evaluation studies and provide feedback, and in return will be offered a number of benefits, including first access to new knockout models and ordering priority and fulfilment, as well as participating in the establishment of the research and development pipeline for this technology.

Initially, SAGE Labs will be working on knockout rat models that target more than 20 genes across a number of research areas. One example is neurobiology, where knockout rat models are being developed with conditions such as schizophrenia, Parkinson's disease, obesity and Alzheimer's.

Looking ahead, Sigma-Aldrich sees significant potential for applications that use ZFN technology to develop rodent models for most types of human disease that could theoretically reduce research times by years and thus save a significant number of lives.