The Dow group used the method to introduce two changes into maize, a plant that is often used for animal feed. The researchers targeted a gene involved in the production of phytates, chemicals in maize that most animals can’t digest, and used the gene as a landing pad to insert another gene that gives the plant tolerance to herbicides. At the same time, they disrupted the target gene so that the plant produces fewer phytates, which Shukla says can also accumulate as waste in water runoff from farms. The ability to “stack” desired traits in this way is not easily performed with existing technologies.
The academic group used a similar method, developed by the Zinc Finger Consortium, an international team of researchers committed to developing a publicly available platform for engineering zinc finger nucleases. Rather than add a new gene into a plant, the researchers used zinc finger nucleases to introduce an altered genetic sequence into an existing gene in tobacco plants; the protein encoded by the gene is a target of herbicides, and the alterations make the plants herbicide resistant. Voytas says that being able to make such subtle changes within a gene will give researchers a new way to study plant biology.
The method still requires generating multiple plants and screening them to find the ones that were successfully altered, but the numbers are in the tens or hundreds, rather than the thousands or tens of thousands. Shukla estimates that the technology cuts the time required to engineer a plant by about half. The method also requires the creation of zinc finger nucleases that are specific to a particular application. Shukla says that Dow is already employing its platform for creating the molecules across its internal products as well as in academic research projects, and it’s planning to license the technology for academic, commercial, and humanitarian use. Voytas says that the Zinc Finger Consortium is making its method available publicly and will be offering training sessions in the technique.
Matthew Porteus, a biochemist at the University of Texas at San Antonio, who wrote an accompanying editorial in Nature, says that the two papers are the first examples of investigators who have picked a gene of interest, designing zinc finger nucleases for that gene, and using the nucleases to create specific modifications in plants. Porteus, who has been investigating zinc finger nucleases as a method for gene therapy in humans, says that interest in zinc finger nucleases has been growing in the past few years. They are being used as a way to create precise mutations in zebra fish, and a human clinical trial is just beginning that will test the use of zinc finger nucleases to create genetic alterations in the T cells of patients with HIV, with the hope of making their cells better able to fight infection.