Scanning electron micrograph of a human T cell from the immune system of a healthy donor. By Sara Reardon and Nature magazine The...
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| Scanning electron micrograph of a human T cell from the immune system of a healthy donor. |
The approach involves using enzymes to destroy a gene in the immune cells of people with HIV, thereby increasing resistance to the virus
A clinical trial has shown that a gene-editing technique can be safe and effective in humans. For the first time, researchers used enzymes called zinc-finger nucleases (ZFNs) to target and destroy a gene in the immune cells of 12 people with HIV, increasing their resistance to the virus. The findings were published March 5 in The New England Journal of Medicine.
“This
is the first major advance in HIV gene therapy since it was
demonstrated that the ‘Berlin patient’ Timothy Brown was free of HIV,”
says John Rossi, a molecular biologist at the Beckman Research Institute
of the City of Hope National Medical Center in Duarte, California. In
2008, researchers reported that Brown gained the ability to control his HIV infection after they treated him with donor bone-marrow stem cells that carried a mutation in a gene called CCR5. Most HIV strains use a protein encoded by CCR5 as
a gateway into the T cells of a host’s immune system. People who carry a
mutated version of the gene, including Brown's donor, are resistant to
HIV.
But similar treatment is not feasible for most people with HIV:
it is invasive, and the body is likely to attack the donor cells. So a
team led by Carl June and Pablo Tebas, immunologists at the University
of Pennsylvania in Philadelphia, sought to create the beneficial CCR5 mutation in a person’s own cells, using targeted gene editing.
Personalized medicine
The researchers drew blood from 12 people with HIV who had been taking antiretroviral drugs to keep the virus in check. After culturing blood cells from each participant, the team used a commercially available ZFN to target the CCR5 gene in those cells. The treatment succeeded in disrupting the gene in about 25% of each participant’s cultured cells; the researchers then transfused all of the cultured cells into the participants. After treatment, all had elevated levels of T cells in their blood, suggesting that the virus was less capable of destroying them.
The researchers drew blood from 12 people with HIV who had been taking antiretroviral drugs to keep the virus in check. After culturing blood cells from each participant, the team used a commercially available ZFN to target the CCR5 gene in those cells. The treatment succeeded in disrupting the gene in about 25% of each participant’s cultured cells; the researchers then transfused all of the cultured cells into the participants. After treatment, all had elevated levels of T cells in their blood, suggesting that the virus was less capable of destroying them.
Six
of the 12 participants then stopped their antiretroviral drug therapy,
while the team monitored their levels of virus and T cells. Their HIV
levels rebounded more slowly than normal, and their T-cell levels
remained high for weeks. In short, the presence of HIV seemed to drive
the modified immune cells, which lacked a functional CCR5 gene, to proliferate in the body. Researchers suspect that the virus was unable to infect and destroy the altered cells.
“They
used HIV to help in its own demise,” says Paula Cannon, who studies
gene therapy at the University of Southern California in Los Angeles.
“They throw the cells back at it and say, ‘Ha, now what?’”
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