06.11.14 5:00 PM ET
Gene Editing Could Erase HIV
The diagnosis of HIV is not what it used to be. With new lines of therapeutics, patients are living longer than ever before. However, despite our significant accomplishments, the transmission of HIV is still of great concern, and it’s infectious circuitry may be written deep in our genes.
What if it was our own genetic code that was responsible for inviting HIV into the life of a cell cycle? What if the only way HIV could insert itself into a healthy cell is by taking advantage of a vulnerable line of human genetic code? If you burn the invitation, do you prevent transmission or replication?
Professor Yuet Kan has led his research team at the University of California San Francisco to achieve just that. Using a technique known as gene editing, Kan’s group has singled out the one gene—the one invitation—that codes a protein known as CCR5. For HIV, CCR5 is the key site of entry into CD4+ T-cells—white blood cells the virus uses to replicate itself for survival, proliferation, and transmission.
For years, gene editing has allowed scientists to manipulate genetic material, but only recently has the technique achieved the precision and flexibility necessary to facilitate Professor Kan’s outcomes. His team uses a new gene-editing system known as CRISPR/Cas9. CRISPR, which stands for clustered regularly interspaced short palindromic repeats, describes the circumstance-specific site within a cell’s huge expanse of DNA that Kan is able to identify and latch onto to insert his desired CCR5 variation. Cas9 are the molecular scissors that cut out what he does not like: the normal CCR5 that welcomes in HIV.
The value of rewriting the gene for CCR5 has been known for quite some time. In 2006 Timothy Ray Brown, a leukemia/HIV patient, was given a bone marrow transplant that allowed him to wean off HIV treatment. The donor was known to have a benevolent double-mutation in CCR5, effectively conferring the donor and Brown immunity to HIV virus’ entry.
Brown’s story was a beautiful finding, but it left scientists struggling to identify a solution to the worldwide HIV/AIDS epidemic that affects 35 million people annually. Only 1 percent of the Caucasian population exhibits the double-CCR5 mutation that conferred these beneficial outcomes, and bone marrow donations are very complex as it stands. These restrictions would leave an extraordinarily rare group of donors to work with. What Kan’s work offers is a way of giving scientist control, allowing them to place mutated CCR5 into cells whenever they want and into whoever needs it.
In lieu of bone marrow transplants, scientists hope to use stem cells to serve as the future vectors of mutant CCR5 proteins. Stem cells known as induced pluripotent stem (iPS) cells have been available since 2006, leaping over ethical concerns that previously hindered research with embryonic stem cells.
Classically, by turning on/off several genetic switches, scientists can revert cells to a less specialized stage. This regression allows them to be reprogrammed into new cell types: neurons, heart cells, liver cells—even blood cells that carry double-mutant CCR5. Since those reprogrammed blood cells would be derived from the same HIV patient who is to receive them back in the form of a blood transfusion, and the blood would hypothetically offer a perfect match.
Kan’s work with CRISPR/Cas9 is likely just one of many successes of gene editing. As with HIV-entry, the root causes of other relatively common diseases such as sickle cell and cystic fibrosis have long been attributed to a single protein. With such a robust gene-editing technique now available and possibly more to come, scientists are one step closer to dependable gene replacement therapy.
If scientists can find the right switches in iPS cells to turn off and on and shut down vulnerable lines of genetic code, then hopefully the door to HIV will soon be closed.