New Technique to Manipulate Genetic Material Developed by Consortium

A multi-institutional team of researchers has developed a powerful tool for genomic research and medicine, which should allow them to generate synthetic enzymes that can target and manipulate DNA sequences for inactivation or repair.

The potential for discovery is significant, according Dan Voytas, Ph.D., director of the Arnold and Mabel Beckman Center for Transposon Research (Minneapolis, MN, USA) at the University of Minnesota, and coinvestigator of the research. In human therapeutics, researchers may aim to correct genetic disorders or diseases, and in plants, scientists may devise crops that are more resistant to pathogens, yield more product, and better combat stress.

In the July 25, 2008, issue of Molecular Cell, researchers including Dr. Voytas described an efficient method to induce specific genomic modifications in many types of cells--including plants and humans. This is the first time the method will be publicly available and free to researchers. "This method is going to be a turning point in the way we manipulate genomes,” Dr. Voytas said. "It will allow any researcher to make a change to genetic material.”

More specifically, the study showed researchers how to engineer customized zinc-finger nucleases (ZFNs), which can be used to induce specific genomic modifications in many types of cells. "Recent work has shown that ZFNs can alter genes with high efficiency in cells from plants or model organisms like fruit flies, roundworms, and zebra fish, and in human cells,” said J. Keith Joung, M.D., Ph.D., assistant professor of pathology at Harvard Medical School (Cambridge, MA, USA) and director of the molecular pathology unit at Massachusetts General Hospital (MGH; Boston, MA, USA), lead investigator of the study. "Our method will enable academic researchers to rapidly create high quality ZFNs for genes of interest and will stimulate use of this technology in biological research and potentially gene therapy.”

Currently available methods for generating ZFNs are either inefficient or exceed the capabilities of all but a handful of laboratories worldwide. Dr. Morgan L. Maeder, from the Joung lab, reported that the new technique, called OPEN (Oligomerized Pool ENgineering), could rapidly generate ZFNs that induce alterations at sites in three biologically significant human genes and a plant gene. ZFNs made by the new OPEN technique, which utilizes a new archive of reagents that will be made publicly available by the Zinc Finger Consortium, were so efficient that they could modify as many as four copies of a gene in human cells and two copies in plant cells.

"Our study provides the first evidence that ZFNs can make specific changes in plant genes with high efficiency and opens a new avenue for plant genetic modification,” Dr. Voytas said. At the University of Minnesota, Dr. Voytas and his team are interested in modifying plant genes for crop improvement.

"With the development of OPEN, many more academic labs will be able to construct, test, and use ZFNs in their biological research projects,” Dr. Joung said. "OPEN should also stimulate additional research into the potential application of ZFNs for gene therapy of single-gene disorders, such as sickle cell anemia and cystic fibrosis.”

The Drs. Joung and Voytas teams worked jointly with labs from Charite Medical School (Berlin, Germany), the University of Iowa (Iowa City, IA, USA), Iowa State University (Ames, IA, USA), and the University of Texas Southwestern Medical Center (Dallas, TX, USA) to develop and validate this new technology. The participating teams are members of the Zinc Finger Consortium, an international group of investigators committed to the development of engineered zinc-finger nuclease technology.

Related Links:
Mabel Beckman Center for Transposon Research
Harvard Medical School
Zinc Finger Consortium