A group of scientists report the creation of the first genetically modified rats using Sangamo Biosciences zinc finger nuclease (ZFN) technology. The rats had permanent, heritable gene mutations, which paves the way for the development of novel genetically modified animal models of human disease, according to the researchers.
“Until now, rat geneticists lacked a viable technique for knocking out, or mutating, specific genes to understand their function,” states Howard Jacob, Ph.D., director of the human and molecular genetics center at the Medical College of Wisconsin. “This study demonstrates that ZFN technology bypasses the current need to conduct cumbersome experiments involving nuclear transfer or embryonic stem cells and allows rapid creation of new animal models.”
The study appeared in the July 24 issue of Science and is titled “Knockout Rats via Embryo Microinjection of Zinc Finger Nucleases.” Besides investigators from the Medical College of Wisconsin and Sangamo, the research team included scientists from Sigma-Aldrich, Open Monoclonal Technology, and INSERM.
They used ZFNs to knock out an inserted reporter gene and two native rat genes without causing measurable effects 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 generate heritable, knockout mutations in a whole organism.
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. ZFNs have reportedly been used to knock out specific genes in fruit flies, worms, cultured human cells, and zebrafish embryos. They are also currently in clinical trials for the treatment of HIV/AIDS.
Sigma-Aldrich, the sole source of commercial zinc finger nucleases for the research community, markets Sangamo’s ZFN technology through its CompoZr™ line of products and services.