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Researchers Create First Targeted Knockout Rats Using Zinc Finger Nuclease Technology
Date:7/23/2009

s on other genes. Importantly, offspring of the ZFN-mutated rats also carried the modifications, demonstrating the genetic changes were permanent and heritable. Together, these results demonstrate the ability to deliver engineered ZFNs into early-stage embryos and rapidly generate heritable, knockout mutations in a whole organism.

Rats are physiologically more similar to humans than are mice for many traits and are ideal subjects for modeling human diseases. Extensive genetic characterization has revealed that approximately 90 percent of the rat's 25,000-30,000 estimated genes are analogous to those in humans and mice, and their larger size makes them a superior model for drug-evaluation studies using serial sampling. Generating rats with knockout mutations has been a major challenge, but the new technique will increase the rat's usefulness in research pertaining to physiology, endocrinology, neurology, metabolism, parasitology, growth and development and cancer. Along with his colleagues, Dr. Jacob's team hopes to use knockout rats to gain a better understanding of disease processes related to hypertension, heart disease, kidney failure and cancer.

ZFNs are engineered proteins that induce double strand breaks at specific sites in an organism's DNA. Such double-strand breaks stimulate the cell's natural DNA-repair pathways and can result in site-specific changes in the DNA sequence. Previously, ZFNs were used to knock out specific genes in fruit flies, worms, cultured human cells and zebrafish embryos and are now in human clinical trials for the treatment of HIV/AIDS. This is the first example of successful gene editing in mammalian embryos using this technology.

"Our ZFN technology is widely applicable across species," stated Philip Gregory, D.Phil., Sangamo's vice president of research. "Used in conjunction with standard laboratory techniques, ZFNs provide a powerful solution to the challenge
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SOURCE Sigma-Aldrich
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