BY Benjamin Ryan

October 08 2009 9:00 AM ET

The Obstacles
Current anti-HIV gene research largely involves variations on a similar theme. First, the scientists remove a collection of immune cells from an HIV-positive person's body, be they T cells or the stem cells that manufacture them. Second, they use what are called vectors to insert one or more new genes into those cells. These vectors are actually viruses themselves, and they have the capacity to cut and paste DNA strands to insert new genetic instructions. The modified cells are then put back into the patient. Finally, a waiting game follows as researchers see if the cells absorb well into the immune system, how long they last, and how successful they are at fighting HIV.

In an ideal setting, perhaps bordering on science fiction, the reprogrammed cells would permanently change the immune system. Scientists more realistically anticipate such a treatment would likely have to be repeated once or twice a year.

Like combination antiretroviral therapy, which uses different classes of medications to attack the virus at various stages of its life cycle, the best gene therapy will probably have multiple targets. John Zaia and John Rossi, researchers at City of Hope, a cancer research center in Southern California, are studying patients who are undergoing treatment for AIDS-related lymphoma. As with any bone marrow transplant treatment, a new immune system is infused into the patient after the other is wiped out by chemotherapy. Zaia and Rossi are attempting to manufacture a number of immune cells whose genetic codes have been rewritten in three different ways to better fight HIV and to include those cells with the transplant.

Like many others in his field of study, Zaia says the case reported in 2008 of the German man who was effectively cured of HIV after receiving a bone marrow transplant during treatment for leukemia proves the genetic method of attacking HIV can work. Replicating that one case, however, is not practical. There is a one-in-10-million chance of finding a donor who is both a match for any one bone marrow type and who has the particular genetic abnormality that is resistant to HIV infection, as was the case with this man. (Only 1% to 2% of humans have CD4 T cells that lack the CCR5 coreceptor, which most strands of HIV need to latch on to in order to enter a T cell. These people are thought to be naturally resistant to HIV infection.) The trick is finding a way to manufacture such resistance synthetically and then successfully transplanting the cells without the need for potentially lethal chemotherapy.

For example, Carl June, a cancer researcher at the University of Pennsylvania, is attempting both to create CD4 T cells that lack the CCR5 coreceptor and also to train CD8 T cells to recognize HIV more quickly and kill the virus more effectively.










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