Two unsuspecting farm animals have helped to demonstrate the increasing accuracy of genetic engineering techniques. The first is a cow that produced hypoallergenic milk after researchers used RNA interference to block the production of an allergy-inducing protein, as reported today (October 2) in PNAS. The second, reported in another paper in the same issue, is a pig that could be a model for atherosclerosis after researchers used an enzyme called TALEN to silence a gene that usually helps to remove cholesterol.
Researchers have long struggled to remove cow milk's allergy-inducing protein, beta-lactoglobulin, which can cause diarrhoea and vomiting in children. They were previously unable to introduce foreign genes precisely enough, however, so they could never quite successfully replace the gene that codes for beta-lactoglobulin with a defective form.
But scientists at AgResearch in Hamilton, New Zealand, worked with molecules that interfere with messenger RNA (mRNA), which helps translate genes into proteins. They found microRNA (miRNA) in mice that targeted beta-lactoglobulin mRNA, so they inserted DNA encoding a version of this miRNA into the genomes of cow embryos. Out of 100 embryos, one calf produced beta-globulin-free milk. “This isn’t a quick process,” Stefan Wagner, a molecular biologist at AgResearch, told Nature. One problem is that RNA interference can’t eliminate the protein completely because some mRNA slips through.
Another technique could speed up the process. TALENs are enzymes that target and cut out a specific DNA sequence from the genome. As the break is repaired, mutations are introduced that scramble the targeted gene, leaving it unable to function.
“The TALEN technology is staggeringly easy, quick, and leaves no mark in the genome,” researcher Bruce Whitelaw, told Nature. Whitelaw, a molecular biologist at the Roslin Institute near Edinburgh, UK, and colleagues at Recombinetics, a livestock genetics company in Minneapolis, Minnesota, used TALENs to disrupt genes encoding low-density lipoprotein (LDL) receptors in pigs. Without those receptors, which remove LDL from the blood, the pigs develop atherosclerotic arteries. Such pigs could be reliable models for biomedical researchers studying human atherosclerosis.
Clarification (October 8): Bruce Whitelaw worked as part of a team to produce the GM pigs mentioned in this story. The Scientist has added that information and regrets the omission.