March 22, 2021

In an effort to study more treatments for HIV, researchers at the Wisconsin National Primate Research Center are focusing on a gene that cured two men of HIV.

Both men – Timothy Brown and Adam Castillejo – received bone marrow stem cell transplants to treat their leukemias. The cells came from donors with a rare genetic mutation that left their white blood cell surfaces without a protein called CCR5.

“Without CCR5, HIV can’t attach to and enter cells,” said Ted Golos, a University of Wisconsin–Madison professor of comparative biosciences and obstetrics and gynecology.

The mutation occurs naturally in fewer than 1 percent of people, suggesting it may not be associated with only positive health outcomes. So the University of Wisconsin researchers are looking to an animal model at the Wisconsin National Primate Research Center to better understand the mutation.

“Given interest in moving forward gene-editing technologies for correcting genetic diseases, preclinical studies of embryo editing in nonhuman primates are very critical,” said Igor Slukvin, UW–Madison professor of pathology and laboratory medicine.

Golos, Slukvin and colleagues used CRISPR to edit the DNA in newly fertilized cynomolgus macaque embryos. They delivered the CCR5-absent gene to one-cell fertilized embryos, thinking if they made the edit in the early embryo it should propagate through all cells as the embryo grew. That’s exactly what happened one-third of the time.

The researchers’ next goal is to transfer the embryos into surrogates to produce live offspring carrying the mutation. With specially selected  monkeys carrying the CCR5 mutation, the researchers would have a reliable way to study how successful the transplants are against the simian immunodeficiency virus (SIV), which works in monkeys just like HIV does in humans.

Anti-retroviral drugs have greatly increased survival in people with HIV, but they are not equally effective in all patients, and there are long-term consequences to consider. Studying an alternative approach might benefit more patients in the short-term while researchers seek long-term solutions to protect people from HIV infection.