In a promising new study, a team of scientists successfully edited the genome of stem cells to precisely mimic a relatively rare mutation that confers natural resistance to HIV infection. If these mutant cells can be safely transplanted into patients, the researchers believe this approach could eventually lead to a functional cure of HIV infection. The study has been published in published in Proceedings of the National Academy of Sciences of the United Stated of America.

A couple of weeks ago we shared the incredible story of the 2008 Berlin Patient, Timothy Ray Brown, who was cured of HIV infection by receiving a stem cell transplant from a donor possessing a mutation which naturally confers HIV resistance. The mutation, which is called CCR5Δ32, involves a deletion of 32 base pairs of DNA in the gene that produces a type of receptor important in HIV infection called CCR5.

Although HIV mainly uses a receptor found on white blood cells called CD4 in order to gain entry into target cells, it also requires a second receptor which is usually CCR5. The CCR5Δ32 mutation results in the production of an abnormal receptor that does not localize to the outside of cells, therefore impairing the ability of HIV to enter host cells. However, it is only individuals who are homozygous (carry two copies) for this mutation that are immune to HIV infection.

By transplanting CCR5Δ32 stem cells into Brown, doctors were able to cure him of HIV infection. While this dramatic treatment is not a viable option in the vast majority of circumstances due to the high risks and costs involved, there may be light at the end of the tunnel.

Inspired by this infamous case, a team of scientists led by the University of California San Francisco’s Yuet Kan set out to replicate this result without needing to source compatible stem cell donors with the mutation.

To do this, the researchers turned to a genome editing system called CRISPR-Cas9 which is based on an immune system used by various bacteria and archaea to confer resistance to viruses. They used this system to accurately snip out a piece of target DNA in induced pluripotent stem cells (iPSCs) which exactly mimicked the natural CCR5Δ32 mutation.

They then differentiated these mutant iPSCs into two different types of immune cell and, as predicted, they were completely resistant to HIV infection in the lab.

If the technique was put into practice, a patient's own cells could be used as a source of iPSCs as a form of personalized medicine. According to New Scientist, Kan does not intend on differentiating the mutant iPSCs into the main type of white blood cell that HIV infects, called a CD4⁺ T cell. Instead, he will differentiate them into a type of precursor cell that is capable of turning into any type of blood cell.

If these mutant stem cells could be safely transplanted into HIV infected recipients in a similar manner to the Brown case, then in theory this technique could eventually lead to a functional HIV cure. But this is no mean feat as successfully transplanting stem cells is notoriously difficult, and rigorous safety tests will have to be conducted first before the cells can go anywhere near a patient.  

The team therefore has a long way to go before this approach can be used in a clinical setting, but it is a promising concept that could potentially also be applied to correct other genetic mutations.