Using a recently developed gene-editing technique, researchers may have found a way to block HIV from invading people’s immune systems. The work, published in Cell Stem Cell last week, is an important first step in editing out what makes our cells vulnerable to the virus. It also makes it possible for a person's own immune cells to attack HIV -- without being susceptible to it.
HIV specifically targets T cells, one of the major cells of our immune system. The virus enters through a gene receptor called CCR5, which basically serves as a doorway to the cells. Once inside, HIV replicates, kills off the host cell, and begins to destroy the immune system, leaving the patient vulnerable to opportunistic infections.
With the relatively new CRISPR/Cas9 technology (for clustered, regularly interspaced, palindromic repeats), relevant genes can be precisely edited out of the patient’s own cells. For HIV patients in particular, these would be T cells and blood-forming stem cells called hematopoietic stem and progenitor cells (HSPCs), which give rise to the body’s blood and our entire blood-based immune system.
Using CRISPR, a team led by Harvard Stem Cell Institute’s Derrick Rossi and Chad Cowan successfully knocked the CCR5 receptor out of blood stem cells. “You can take blood-forming stem cells out of a patient, edit them, and transplant them back," Rossi explains in a news release. The edited HSPCs then gave rise to normal, functioning blood cells that don’t have CCR5.
"We're removing the doorway that HIV uses to get into cells,” Cowan tells Time. CCR5-free cells mean HIV-resistant cells.
Additionally, the team did “very, very deep sequencing analysis to show that there were no unwanted mutations,” Cowan explains, so the technique appears to be safe. With an average of 3,400 sequencing passes, compared with the 50 that are usually used for whole-genome sequencing, they found that the system’s risk of making aberrant cuts was effectively zero.
This new approach to HIV therapy could be ready for human safety trials in less than five years. Though, as Cowan adds, “there is obviously much more work to do.” For starters, the history of the HIV/AIDS epidemic is littered with alleged “cures,” and even if this new approach works perfectly without unexpected complications, applying it to parts of the world that are hardest hit will require additional development. Next up, the team will be giving their edited cells to mouse models with human immune systems.