Researchers at the Keck School of Medicine of USC successfully have transplanted blood stem cells modified to be resistant to HIV into mice, allowing the animals to control HIV infections.
If the approach can be translated to human patients, it would enable the long-term generation of HIV-resistant T cells in a patient’s body, and the potential for the patient’s own cells to suppress HIV.
The strategy is explained in a new study published online in the journal Nature Biotechnology.
“This hybrid gene and stem cell therapy shows that it is possible to create HIV resistant immune cells that can eventually win the battle against HIV in vivo,” said principal investigator Paula Cannon, associate professor of molecular microbiology and immunology at the Keck School of Medicine of USC. “We’ve done it at the scale of a mouse, and the challenge now is to see if this can be done at the scale of a human patient.”
The approach targets a gene called CCR5, one of the two gateway molecules that HIV uses to enter human cells. Cannon’s strategy arose from the observation that people with a mutation in a gene called CCR5 are naturally resistant to infection with the most common strains of HIV and do not develop AIDS.
The team used enzymes called zinc finger nucleases — which physically cut DNA — to knock out the the CCR5 gene in human blood stem cells. The researchers transplanted these modified stem cells into mice, where they developed into mature cells of the human immune system, including the T cells that HIV infects. When the researchers then infected the animals with HIV, they found that the mice were able to maintain normal levels of the human T cells and suppress HIV to very low levels, unlike control mice that received unmodified stem cells.
Cannon’s preliminary data on the ability of this anti-CCR5 therapy to control HIV replication has formed the basis of a collaboration between USC, lead institution City of Hope National Medical Center and the biotech company Sangamo BioSciences Inc., which makes the gene-editing technology.
The team received $14 million last year from the California Institute for Regenerative Medicine to develop this novel therapy further in the hope that it may offer lifetime immunity to HIV infection. The grant was awarded as part of the Disease Team Research Awards, aimed at speeding the process of bringing stem cell therapies to clinical trials.
“By engineering CCR5-deficient stem cells, we may allow a patient to produce HIV resistant cells in all of the cell types that the virus infects and for long periods of time,” Cannon said. “If successful, it could one day allow patients to control their HIV without needing to take antiretroviral drugs.”