Several major strides have been made towards a cure for HIV in recent years, and now, researchers from the University of California San Diego (UCSD) may have found a new potential target. In lab tests, the team identified a cellular “switch” that could be turned off to clear out the virus lying dormant inside cells.

Currently, people with HIV undergo a life-long treatment called antiretroviral therapy, which suppresses symptoms and keeps the infection from developing into AIDS. But it isn’t a full cure – the virus can lay dormant inside a patient’s cells, ready to start multiplying again if the treatment is ever stopped.

Finding ways to kill the virus while it lays dormant is the holy grail of HIV research, and now the UCSD team says it’s a step closer to a cure. They found that a particular RNA molecule appears to be elevated in people with HIV, and in tests on cultured cells they showed that silencing or removing it prevented HIV from recurring after antiretroviral therapy was stopped.

The molecule is what’s known as a long non-coding RNA (lncRNA), meaning it doesn’t encode for proteins but instead helps control the switching of genes on and off within a cell. The team has dubbed this particular molecule HIV-1 Enhanced LncRNA (HEAL). Interestingly, the HEAL gene appears to have emerged fairly recently, and it regulates HIV replication in immune cells.

“This is one of the key switches that the HIV field has been searching for three decades to find,” says Tariq Rana, an author of the study. “The most exciting part of this discovery has not been seen before. By genetically modifying a long noncoding RNA, we prevent HIV recurrence in T cells and microglia upon cessation of antiretroviral treatment, suggesting that we have a potential therapeutic target to eradicate HIV and AIDS.”

In experiments on isolated human immune cells in the lab, the researchers either silenced HEAL, or snipped it out of the genome using the gene-editing tool CRISPR-Cas9. In both cases, HIV didn’t re-emerge after the antiretroviral therapy stopped.

“Our results suggest that HEAL plays a critical role in HIV pathogenesis,” says Rana. “Further studies are needed to explain the mechanism that leads to HEAL expression after an individual is infected by HIV, but this finding could be exploited as a therapeutic target.”

Of course, this is a very early test, and it hasn’t yet been performed in animals, let alone humans. Still, it’s an interesting new avenue for research into a potential cure.

And it’s not the only one scientists are investigating. Earlier this year a team used a new type of antiretroviral therapy called LASER ART to suppress the virus, then snipped it out using CRISPR – effectively curing the infection in mice. Another team used stem cells to put a man into long-term remission for only the second time ever – but the treatment itself was dangerous, painful and not likely to be recommended to general patients in its current form.

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Blood cells altered to block HIV have safely stuck around for more than a year and a half after they were transplanted into a volunteer, raising hopes of a more accessible cure.

While it’s not the first time HIV-resistant blood cells have been used to fight the infection, this time researchers used CRISPR in a new way. Their success could open this therapy up as a safe and effective treatment for an even greater number of people.

Encouraged by their results in an earlier study on mice, Chinese researchers genetically modified hematopoietic stem and progenitor cells provided by a donor and transplanted them into a 27-year-old man who had two diagnoses – an acute form of leukaemia and was HIV positive.

In this case, having the blood cancer alongside HIV was a crucial part of the patient being fit for this study, as that allowed the team to use the cell transplantation procedure as treatment, except with an added CRISPR twist.

More than 19 months after the altered cells were transplanted into the patient’s body, the investigation team concluded the new transplant had not only taken hold, but it also hadn’t resulted in any side effects that can be linked with the editing process.

Months after receiving the HIV-resistant donor tissue, the patient stopped taking his course of virus-busting medications so the researchers could check whether the portion of resistant blood cells made any difference in the pathogen’s ability to replicate.

Unfortunately in this case, it wasn’t to be. The man’s viral load began to climb back up again, forcing him to return to his usual assortment of anti-retroviral drugs.

On closer inspection, it turned out the HIV-resistant cells had replaced little more than 5 percent of the patient’s lymphocytes, going some way to explaining the low efficiency of the treatment.

But even if the volunteer still requires ongoing anti-retroviral treatment to manage his infection, the fact the genetically altered donor cells stuck around so long without a problem is counted as a significant win by the research team.

The method used a cutting-edge technology known as CRISPR-Cas9 to break the gene behind a receptor in the white cell’s membrane called CCR5, effectively changing the locks HIV uses to infiltrate and destroy the immune cells.

A mutated version of this receptor already occurs naturally, offering a suitable level of resistance in those fortunate enough to have at least one copy of the variant gene.

Ever since the discovery of this twisted form of the CCR5 receptor, it has been the subject of intense research into future generations of HIV treatments.

Initially researchers focussed on transplanting stem cells from donors with the mutant form of the gene, demonstrating a remarkable level of success some have equated with an actual cure.

Yet advances in DNA editing have tempted a number of researchers to look beyond naturally occurring mutants and artificially produce HIV-resistant versions by knocking out bits of CCR5’s genetic sequence.

In its most controversial form, a Chinese researcher claimed in 2018 to have edited the CCR5 gene in the embryonic cells of twin girls. The infamous study has since highlighted the health risks and ethical challenges associated with gene editing technology, especially on such a fundamental level.

Applied to donated tissues, there still remains fear that CRISPR could unintentionally give rise to significant levels of damage that turn innocent cells into something less benign.

Treading lightly, this latest study set out simply to show whether the transfer of CRISPR-edited blood stem cells could be done safely and efficiently. There’s still a long way to go before we’ll see this kind of therapy being used conventionally, if at all.

Not only do researchers need to find more reliable ways to alter the CCR5 gene, they need to find more effective methods for transplanting the tissue to increase the chance it will contribute a significant number of white blood cells.

Recent studies suggest that having two broken copies of the CCR5 gene might not be so great for life expectancy, even if it does help you avoid an infection with HIV.

Understanding exactly why this is the case would be an important step in demonstrating this kind of treatment is ultimately safe. But the fact remains, tens of millions of people all around the world carry the virus. They come from all walks of life, all ages, with all kinds of bodies.

To put an end to the pandemic, we’ll need treatments that are effective and can suit not just a fortunate handful, but work for all of them.

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Researchers say they have removed HIV from the DNA of mice, an achievement the scientists say could be an early step towards an elusive cure for humans.

The breakthrough, detailed earlier this week in a study credited to more than 30 scientists from Temple University and the University of Nebraska Medical Centre, was made possible by an antiviral drug in combination with the tool called CRISPR that can edit genes.

The researchers eliminated HIV in nine of 23 mice that were modified so their immune systems better mimicked those of humans.

Clinical trials for the gene-editing component of the cure could start as early as next year if the Food and Drug Administration approves them, said Kamel Khalili, one of the study’s senior investigators.

But he and other HIV experts emphasised that there is a big scientific leap from promising results in mice to success in humans.

“We knew what we needed to do, but the technology was unavailable,” Dr Khalili told The Washington Post, saying he and his team had been awaiting a tool like CRISPR to combat a virus that “becomes part of the fabric of our chromosomes”.

With gene editing finally a reality, he said, “the outcome was amazing”.

Once deadly, HIV can now be managed with a treatment called anti-retroviral therapy.

The therapy only keeps the virus in check; without constant medication, the virus will quickly decimate a patient’s ability to fight off sickness.

HIV infects 37 million people worldwide, according to the latest data from the World Health Organisation (WHO), and only about 22 million of those people receive antiretroviral therapy. Nearly one million people died of HIV-related issues in 2017, according to WHO.

Earlier this year, revelations that a second person had seemingly been rid of the virus raised hopes that another patient’s cure 12 years earlier was not a one-off victory.

But scientists cautioned that it was too early to declare the anonymous second patient cured – and that, regardless, the case did not herald a widespread cure for the devastating condition.

Both patients were treated with stem cell transplants, which experts say are risky, bring serious side-effects and would not be preferred for most patients.

Previously, Dr Khalili’s team at Temple had found a way to remove significant amounts of HIV DNA from rats and mice.

But the technique could not completely remove the infection.

So Dr Khalili’s lab joined forces with a University of Nebraska Medical Centre (UNMC) lab attacking the problem in a different way. Together, the scientists combined the gene-editing strategy with a drug designed to beat back HIV.

Howard Gendelman from UNMC said that his team’s experimental drug is engineered to act over a longer time than normal therapies, meaning it can be administered every couple of months instead of every day.

It is also better able to target HIV in the body, he said. It is crucial that gene editing remove every last bit of HIV, he said, and the drug makes that task easier.

“If you can reduce the amount of virus that’s left for CRISPR, the likelihood that the CRISPR will be effective will go up enormously,” he said.

But if Dr Khalili’s team is able to move forward with trials with humans, it will use standard drugs rather than the one developed by UNMC’s lab, since it probably would not be approved yet for use, Dr Khalili said.

Steven Deeks, a professor at the University of California at San Francisco who has worked extensively on HIV, said the use of gene editing to remove HIV from a live animal is a notable step forward.

But he cautioned that using the technique on humans will be far more challenging: scientists will have to grapple with more variations in the virus, more difficulties in delivering the gene-editing technology and the possibility of cutting up human genes while trying to target HIV, he said.

Those are formidable problems, Prof Deeks said, especially with success depending on removing the virus completely.

“For this approach to work, they have to really knock out 100 percent of the genomes – you can’t leave anything behind,” Professor Deeks said. “One of them can reignite the whole process.”

The scientists behind the new study recognise those challenges. Dr Khalili said researchers are in the process of publishing another study on the use of gene editing to target HIV in primates and are hopeful about bringing the solution to human subjects.

But the scientists need to make sure their techniques are safe, he said. They also want to increase their methods’ chances of working from the roughly one-third success rate they saw with mice.

Dr Gendelman said that while modern drugs are good at keeping HIV at bay, a permanent cure would bring big benefits to patients.

Constant drug treatment can contribute to other health complications, he said, and just keeping the pills in your medicine cabinet can invite unwanted scrutiny from family or significant others.

“There’s a tremendous stigma,” he said. “Every time you take those pills you’re reminded that you have HIV.”

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