Pill power

 作者:能偃     |      日期:2019-03-08 10:16:01
By Jonathan Knight THE morning-after pill has given a boost to hopes that gene therapy may one day fulfil its promise of curing disorders such as cancer and diabetes. Modified viruses can be used to deliver genes to lab animals. But controlling genes once they reach their target has been difficult. “There is almost no gene product that you can make continuously without causing some sort of problem,” says Bert O’Malley at Baylor College of Medicine in Houston. So O’Malley wanted a way of switching on a foreign gene inside the body without altering the expression of other genes as well. To do this his team tinkered with a gene-controlling protein that switches on nearby genes when it binds to DNA and when activated by progesterone. They engineered the protein so that it would be activated only by the synthetic progesterone blocker mifepristone, the main ingredient of the morning-after pill, and so that it contained a fragment that binds only to a special short sequence of DNA not found in the human genetic code. To the gene that codes for this designer protein, the team added the nonhuman DNA sequence and the gene for human growth hormone. They inserted the whole sequence into a virus, and injected the virus into mice. The idea was that mifepristone would activate the switching protein, which would bind to the nonhuman DNA and activate the growth hormone gene. When some of the mice were given mifepristone, detectable levels of human growth hormone duly appeared. The dose was 1000 times lower per gram of body weight than is used to induce menstruation in women. When the drug wore off, the gene shut down again (Proceedings of the National Academy of Sciences, vol 96, p 355). The system is quite flexible, O’Malley says: “You can pop out the growth hormone gene and put in any other gene you want.” He expects clinical trials to begin next year, most likely with an anticancer gene. Gary Nabel, a gene therapy researcher at the University of Michigan in Ann Arbor, says the problems with control genes may have scared pharmaceuticals companies away from gene therapy due to safety fears. “Having tools like these will bring a greater degree of safety,