A new technique offers opportunities for minimalist modifications to plant, animal and human genomes
You know that feeling you get when someone is watching you? Daniel Voytas and his colleagues should be getting that feeling a lot these days. The eyes of molecular biologists around the world are on them as they forge ahead on what could well be the next big breakthrough in genetic engineering.
A professor of genetics, cell biology, and development, Voytas came to Minnesota a year ago to head the Center for Genome Engineering. Today, he and his colleagues are hot on the trail of a powerful new approach to singling out genes within an organism’s DNA.
The tool that’s captured their attention uses a type of protein segment known as a zinc finger. Found naturally in some proteins that regulate DNA transcription and other cellular activities, zinc fingers are adapted to target and bind to precise DNA sequences in the genome. For genome engineers, that’s a marvelous capability: If you can figure out how to custom-make zinc fingers that latch onto a specific gene of your choice, there’s virtually no limit to what you can do with that gene, from learning what it codes for to boosting its capabilities to—in the case of genetic disorders—replacing a faulty version with a corrected copy.
Voytas became interested in zinc fingers in 2003, when investigators reported using using them to modify specific genes in fruit flies and humans. One point of frustration in developing the technology has been finding a robust method for making proteins containing zinc fingers that target specific genes. Last year, Voytas and his colleagues published a report of a new technique for custom-making DNA-cleaving, zinc-finger-containing proteins called zinc finger nucleases (ZFNs), along with specs on 37 ZFNs his team had constructed to alter genes at 11 sites in humans and other species. In April, he and his colleagues published a report in Nature showing that the method could be used to make specific changes to plant genomes with high efficiency.
U of M scientists and others are now lining up for tailor-made zinc fingers that fit their own research needs. In model organisms such as fruit flies and zebrafish, ZFNs could enhance basic understanding of gene function. ZFNs also hold promise for engineering plant genes for better food, fiber or fuel production and repairing faulty human genes such as those that cause cystic fibrosis or create a predisposition to cancer.
With colleagues at Harvard, Voytas has established an international Zinc Finger Consortium to allow scientists to share information that will hasten the application of zinc fingers to real-world problems. In addition, he and colleagues at the University of Minnesota are setting up capacity within the center to custom-make ZFNs.
“There are still a lot of challenges,” says Voytas. “But it’s worth the frustration to work out the bugs. Our method clearly opens a door.” — Mary Hoff
