Could CRISPR cure HIV someday?

In a groundbreaking clinical trial, researchers are evaluating the safety and efficacy of EBT-101, a revolutionary gene therapy designed to potentially cure human immunodeficiency virus (HIV) infections with just one dose. Utilizing CRISPR-Cas9 gene editing, EBT-101 targets latent HIV infections, marking a significant advancement in HIV treatment.

The ongoing trial, representing the first-ever attempt at gene-editing treatment for HIV in humans, involves 500,000 volunteers. Initial data suggests that EBT-101 is safe at the tested doses, but the crucial question of whether it effectively cures HIV remains unanswered.

HIV, a global public health concern with approximately 39 million affected individuals in 2022, lacks a readily available cure or vaccine. EBT-101, described as an “important step forward” by Thomas Hope, CEO of the UK Biobank, holds the potential to revolutionize HIV treatment by addressing latent HIV reservoirs within human cells.

The unique approach of EBT-101 involves multiple guides targeting various sites in the genome, allowing the removal of large sections of latently integrated HIV DNA. Kamel Kahlili, a professor at Temple University and co-founder of Excision BioTherapeutics, emphasizes the therapy’s safety, with initial results showing no toxic effects or serious adverse events in treated patients currently on cART (combination antiretroviral therapies).

However, cautious optimism prevails, with experts highlighting the need for further testing to ascertain the therapy’s ability to effectively target latent HIV cells and control HIV in humans. Off-target effects, a concern associated with CRISPR treatments, will be closely monitored, as EBT-101 targets multiple sites in the genome.

The next phase of the trial will involve testing additional doses of EBT-101 for safety, followed by assessing whether the virus remains suppressed when patients are taken off cART. Purposeful treatment interruptions, essential for determining remission, will be balanced with inherent risks.

Long-term follow-up studies spanning 15 years will provide insights into potential adverse effects. While the initial safety results are promising, researchers emphasize the need for caution and acknowledge the substantial work ahead to validate the therapy’s efficacy in combating HIV.