Breaking News:New gene-editing method cuts HIV DNA from infected cells across strains – The South First– What Just Happened

For the four crore people living with HIV worldwide, this opens the possibility of a cure rather than lifelong treatment that only suppresses the virus.

Synopsis: A new CRISPR-based gene-editing approach has been shown to cut out HIV genetic material from infected cells in laboratory models, raising the possibility of a cure for the crores of people living with the virus worldwide. Researchers designed the system to target stable regions shared across thousands of HIV strains and achieved up to 100 percent viral excision in some experiments. But for now it remains a proof of concept, with several barriers to overcome before it can become a viable treatment.

The Human Immunodeficiency Virus (HIV) is perhaps the most lethal virus known to infect humans. It attacks white blood cells, weakening the immune system’s ability to fight infection. Without treatment, HIV can progress to its most advanced stage: AIDS (Acquired Immunodeficiency Syndrome).

There is no cure for HIV. One reason is that the virus embeds itself in the DNA of infected immune cells. Once integrated, it can lie dormant beyond the reach of antiretroviral drugs. It also mutates rapidly. This constant mutation creates diverse strains, helps the virus evade the immune system, and increases resistance to treatment.

Gene-editing tools such as CRISPR-Cas9 have been used to remove out this dormant viral DNA from infected cells before. But the sheer number of strains—more than 79,000 documented variants—has made this approach impractical as a treatment.

Recently, researchers at the University of Nebraska Medical Center in the United States have a breakthrough. They designed a version of the tool that accounts for viral diversity, reducing, and in some cases fully excising, the virus in laboratory models.

The findings, published in Lancet eBioMedicine, are proof of concept. They show that, in principle, HIV’s genetic material can be precisely removed from infected cells. For the four crore people living with HIV worldwide, this opens the possibility of a cure rather than lifelong treatment that only suppresses the virus.

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Cutting across strains

To overcome HIV’s mutation barrier, the team at Nebraska, led by Dr Jonathan Herskovitz, built their guide RNAs from a consensus sequence drawn from 4,004 HIV-1 strains. They focused on regions that remain stable across variants.

They settled on a gene called tat, which drives viral replication. Because tat overlaps with other genes, rev and gp41, a single well-aimed cut could knock out up to five viral genes at once. They named their guide RNA system TatDE.

In laboratory experiments across seven HIV strains, TatDE reduced viral replication by an average of 82 percent. When delivered into latently infected T cells using lipid nanoparticles, the same tiny fat bubbles that carry mRNA in Pfizer and Moderna’s Covid-19 vaccines, the system achieved up to 100 percent viral excision in certain models. Critically, the team detected no off-target edits in human DNA.

“The combination of diverse strain-inactivating TatD and tri-exon-directed TatE gRNAs prompted maximal suppression of HIV-1 replication by CRISPR-Cas9,” the authors wrote. “Further refinement of these methodologies will advance the utility of gene therapy in eliminating latent viral infection from infected hosts across the globe.”

The risk of viral reassembly

Removing the virus does not always end the threat. A separate study by researchers at the University of Pisa, led by Dr Michele Lai, showed that when HIV was cut out of infected cells, it did not simply dissolve. Their findings were published in the Journal of Virology. 

Instead, the excised viral DNA folded back on itself, forming small rings, circular molecules that lingered inside the cell for up to two weeks. In some cases, two of these rings joined and reconstructed working viral machinery.

When the researchers introduced the viral proteins Tat and Rev into these cells, proteins that could arrive through a second infection, the circular DNA resumed activity. It produced viral RNA, measurable levels of the HIV protein p24, and in one experiment generated low levels of infectious particles.

“We provide evidence that if the HIV-1 genome is excised as a single fragment, it persists and reorganises in concatemers,” the authors wrote.

“This work stresses the importance of implementing CRISPR-Cas9 strategies in vivo to achieve cleavage of the HIV-1 genome at multiple sites and in all cells.”

In plain terms, cutting the virus out once at a single site may not be enough. If fragments remain intact, they can reorganise and, under the right conditions, attempt a return.

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Delivery is the next barrier

A further problem could limit this breakthrough as a viable treatment: being able to target the correct cells.

The Nebraska researchers tested lipid nanoparticles measuring about 180 nanometres, roughly 500 times smaller than a human hair. Loaded with the TatDE payload, these particles entered macrophages, moved through the cell’s internal transport system, reached the nucleus and delivered the CRISPR components. The macrophages then resisted HIV infection. Confocal microscopy confirmed the cargo reached its target.

Macrophages matter because they circulate through every organ, including the lymph nodes, brain tissue and gut, and are one of HIV’s most persistent hiding places. That reach makes them hard to target and has long been one of gene therapy’s toughest problems.

Meanwhile, in Melbourne, researchers at the Doherty Institute announced a separate advance that addresses the same challenge. They developed a new type of lipid nanoparticle, LNP X, that can deliver mRNA into a category of white blood cell that had previously resisted such particles.

“We were overwhelmed by how night and day the difference was — from not working before, and then all of a sudden it was working,” said Dr Paula Cevaal, co-first author of the study, published in Nature Communications. “Our hope is that this new nanoparticle design could be a new pathway to an HIV cure.”

An unanswered question

Efforts to use CRISPR to treat HIV have been under way for years. In 2023, MIT Technology Review reported that three volunteers who underwent CRISPR-based therapy by Excision BioTherapeutics showed no serious side effects after 48 weeks.

But the new research does not answer a key question. Dr Jonathan Stoye, a retrovirologist and emeritus scientist at the Francis Crick Institute in London, raised it in an interview with the BBC:

“One big unknown remains. Do you need to eliminate the entire reservoir for success, or just the major part? If just 10 per cent of the latent reservoir survives, will that be sufficient to seed new infection? Only time will tell.”

The Nebraska researchers acknowledge that their system needs validation against additional HIV strains and clades. Whole-genome sequencing must confirm there are no off-target edits in unexamined regions of DNA. Precision-targeted nanoparticles must reach every infected cell in the body, including T cells, macrophages and tissue reservoirs that current antiretroviral drugs struggle to penetrate.

“Every infected cell must be excised in order to cure HIV,” the Nebraska team wrote, a sentence that captures both the ambition and the scale of what remains.

(Edited by Dese Gowda)