Sigma-Aldrich develops knockout rats

By Nick Taylor

- Last updated on GMT

Related tags Dna Genetics

Sigma-Aldrich is using a novel methodology to create rats with targeted gene deletion in as little as four months, which it believes could eliminate years of research and improve drug development.

A rat with gene deletion, often referred to as a knockout rat, can more closely mimic human diseases and provide a superior model for preclinical research. This can help cut development time and further research into hard to treat diseases.

The rats will be developed at the Sigma-Aldrich Genetic Engineering (SAGE) labs in St Louis, Missouri, US using its CompoZr Zinc Finger Nuclease (ZFN) gene editing technology.

ZFN’s effectiveness in producing knockout rats with permanent, heritable gene mutations was demonstrated in a research paper published in the journal Science ​on July 24.

This was the culmination of research supported by the Medical College of Wisconsin, Milwaukee, US, Sangamo Biosciences, Sigma-Aldrich, Open Monoclonal Technology (OMT) and INSERM.

Howard Jacob, of the Medical College of Wisconsin, explained: "Until now, rat geneticists lacked a viable technique for "knocking out," or mutating, specific genes to understand their function​."

He added that the ZFN technology “bypasses the current need to conduct cumbersome experiments… and allows rapid creation of new animal models​".

These improvements will allow researchers at SAGE to develop knockout rats in as little as four months, according to Sigma-Aldrich, which is about one third of the time required using traditional techniques.

Further development

Initial research will focus on developing rats for use in furthering treatments for toxicology, neuroscience, cardiovascular and inflammatory diseases. Sigma-Aldrich selected these diseases because it believes they will benefit immediately from the availability of knockout rats.

Jacob is planning to use knockout rats to improve understanding of disease processes related to hypertension, heart disease, kidney failure and cancer. OMT has used ZFN commercially to inactive the gene encoding for immunoglobin M, which is used in antibody production.

Research into gene deletion has focused on rats because of the advantages they have as research models, such as similarity to humans for many traits, but ZFN could be used in other animals.

Philip Gregory, Sangamo's vice president of research added that he believes ZFN “will become the method of choice for genome engineering in cells, plants and transgenic animals​".

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