Can Gene Editing Cure HIV?

Researchers at the University of California, San Francisco, have developed a method to create HIV resistance by editing the genes of a type of cell called induced pluripotent stem cells (iPSCs).

Previous research had revealed that approximately 1 percent of people of European descent have a genetic mutation that alters the gene for CCR5, a protein that the virus must attach to before attacking white blood cells. The mutation creates misshapen proteins that prevent the virus from being able to enter white blood cells, effectively providing HIV resistance.

The UCSF team, led by Yuet Kan, MD, used the CRISPR-Cas9 system, a highly efficient genome editing method, to “snip” out specific DNA segments in these stem cells and replace them with the mutation. Since iPSCs have the potential to grow into any type of cell in the body, white blood cells grown from this mutated form of stem cell could theoretically function as personalized gene therapy.

However, developing such a treatment for real-world use will take some time. Currently, Kan is wrestling with how to transplant this type of stem cell into patients.

“One of the problems is converting iPSCs into a type of cell that is transplantable,” Kan tells New Scientist.  Instead of growing the iPSCs into the CD4+ T cells that are targeted by HIV, Kan plans to turn them into blood-forming stem cells so that they can generate all of the various cells found in blood.

Still, this tactic, also known as gene editing or gene therapy, holds great potential. Kan’s systems could be used to develop a cure for HIV in as early as three years and “10 years at the most,” says Jeffrey Steinberg, MD, a researcher and founder of the Fertility Institutes. In fact, gene editing could be used to treat a host of viral infections, including meningitis, smallpox, and Ebola, if federal regulators such as the Food and Drug Administration were to “take the handcuffs off doctors,” he says.

In Steinberg’s opinion, one of the major obstacles toward developing this treatment is the reluctance of federal agencies to allow what is, in essence, the genetic modification of human beings. Modern regulatory processes, while essential, can also inhibit the progress of research, Steinberg says, and “somebody’s got to give a little bit of a boot to the government to pay attention to these advances.” Currently, regulators still need to be convinced of the safety of manipulating cells genetically, a mandatory step in creating the mutation that shields a person from HIV.

“That it defeats the virus is known. That’s not even a question anymore,” he says. “The question is, How do you get someone to allow you to put it inside the DNA so that people can start [defeating the virus] for themselves?”

Currently, the United States is looking to the U.K., which could soon become the first nation in the world to permit a groundbreaking type of gene therapy, in this case as a means of combating mitochondrial disease, a debilitating and sometimes fatal condition that is passed to children by their mothers. The technique under debate in the U.K. involves the swapping of DNA between egg donors without the disease and women who have it so the latter can have healthy children. This would also prevent future generations from acquiring the genetic disorder, but any ill effects due to changes in DNA would be passed on as well, so that is a factor authorities are considering in deciding whether to allow the therapy.

However, Steinberg hopes the U.S. will take the lead in advancing gene therapy and provide more resources and funding to institutions like UCSF so they may continue to develop gene therapy and “give victims of HIV the ability to fight the virus and eradicate the virus” for themselves.  He believes that gene therapy, more than vaccines or oral medications, has the greatest potential as a cure for HIV. And its development is within the world’s grasp.

“I am very, very excited about it,” Steinberg says. “It’s like developing a smallpox vaccine. Think of the countless lives that have been saved. And the potential is there."