Trials of gene scissors that cut harmful DNA from cells are showing promise, reducing HIV infections and lighting a path to the treatment of genetic diseases.
The New England Journal of Medicine reports on a stage II clinical trial conducted by the University of Pennsylvania to cut CCR5 genes from people with HIV. CCR5 plays no vital purpose, but allows HIV to enter cells. People with alleles of the gene that prevent it producing a protein are resistant to most strains of HIV. Twelve patients had CD4 T cells removed and the CCR5 gene rendered dysfunctional with zinc-finger nuclease, one of the gene cutting mechanisms being explored.
The paper reports, “One serious adverse event was associated with infusion of the ZFN-modified autologous CD4 T cells and was attributed to a transfusion reaction.” This aside, the results were very positive. The patient's T cells count a week after treatment averaged more than three times the preinfusion count. Not all the cells withdrawn and reinjected were successfully modified, but the ones that were survived much longer when returned to the body.
Most importantly, the paper reports, “HIV RNA became undetectable in one of four patients who could be evaluated. The blood level of HIV DNA decreased in most patients.”
As Popular Science reports, this is just one example of a flurry of progress towards being able to cut unwanted DNA from cells. While the University of Pennsylvania trail involved removing a certain class of cells from the body and treating externally, many projects look towards mechanism that will work internally.
The technology used in the HIV trial is part of an expanding toolkit. Zinc fingers are enzymes that bind to stretches of DNA with great strength. Under a microscope the first versions looked like fingers of a hand. By combining several zinc fingers together researchers have shown it is possible to target specific genes. After adding enzymes bacteria use to cut viruses from their DNA the result is a Zinc Finger Nuclease (ZFN) that can be designed to target specific genes and cut them from genetic code.
For all their potential, ZFN's have been partially displaced in research by Transcriptor Activator-Like Effector Nucleases (TALENs) and Cluster Regularly Interspaced Short Palindromic Repeats (CRISPRs) because they are easier to target to specific genes. The natural concern is that releasing any form of gene scissors onto our DNA will result in off-target effects where genes we really need get cut as well. Various control methods are under investigation but so far the newer, shinier scissors are yet to be released inside a human.
