HIV cure ‘closer than ever’ as scientists wipe out virus for first time in living animals – The Sun
SCIENTISTS are "closer than ever" to finding a cure for HIV after discovering a way to wipe out the virus in living animals for the first time.
Researchers say it marks a critical step towards a possible cure for humans – and clinical trials could begin as early as next year.
Current treatment focuses on the use of antiretroviral therapy, known as ART, which suppresses HIV replication, but does not eliminate the virus from the body.
It's not seen as a cure and requires life-long use because if the treatment is stopped, the virus can renew replication and fuel the development of AIDS.
But researchers at Temple University in Philadelphia and the University of Nebraska say they have come up with a revolutionary gene-editing tool.
The team injected mice with human bone barrow to mimic the immune system and say they were able to eliminate HIV in nine of the 21 animals.
Senior investigator Professor Kamel Khalili, an AIDS expert at Temple University, said: "Our study shows treatment to suppress HIV replication and gene editing therapy, when given sequentially, can eliminate HIV from cells and organs of infected animals."
His team used a technique called CRISPR-Cas9 that can snip faulty DNA with a harmless virus and has been likened to a pair of "molecular scissors".
It combines this with a recently developed therapeutic strategy known as LASER (long-acting slow-effective release) ART.
The technique targets viral "sanctuaries" – maintaining HIV replication at low levels for extended periods of time.
This also reduces the frequency of treatments.
The long-lasting medications were made possible by pharmacological changes in the chemical structure of antiretroviral drugs.
HIV rebound is directly attributed to the ability of the virus to integrate its DNA sequence into the genomes of cells of the immune system, where it lies dormant and beyond the reach of antiretroviral drugs.
In the study, published in Nature Communications, the modified drug was packaged into nanocrystals, which readily distribute to tissues where HIV is likely to be lying dormant.
From there, the nanocrystals, stored within cells for weeks, slowly release the drug.
Dr Khalili explained: "We wanted to see whether LASER ART could suppress HIV replication long enough for CRISPR-Cas9 to completely rid cells of viral DNA."
To test their idea, the researchers used mice engineered to produce human T cells susceptible to HIV infection.
This permitted long-term viral infection and ART-induced latency.
Once infection was established, mice were treated with LASER ART and subsequently with CRISPR-Cas9.
The big message of this work is that it takes both CRISPR-Cas9 and virus suppression to produce a cure for HIV infection
At the end of the treatment period, mice were examined and analyses revealed complete elimination of HIV DNA in about one-third of HIV-infected mice.
Dr Khalili said: "The big message of this work is that it takes both CRISPR-Cas9 and virus suppression through a method such as LASER ART, administered together, to produce a cure for HIV infection.
"We now have a clear path to move ahead to trials in non-human primates and possibly clinical trials in human patients within the year."
Just over a generation ago the world was in the grip of AIDS hysteria, but thanks to modern drugs the picture has transformed.
What are the symptoms of HIV?
Most infected people experience a short illness, similar to flu, two to six weeks after coming into contact with HIV.
These symptoms, which 80 per cent of infected people experience, are a sign that their body is trying to fight HIV. They include:
- Sore throat
- Body rash
- Joint and/or muscle pain
- Swollen glands
After this illness, which normally lasts one to two weeks, HIV sufferers will have no symptoms for up to 10 years – during which time they will look and feel well.
However, the virus will continue to cause progressive damage to a person's immune system.
Only once the immune system is already severely damaged will the person show new symptoms. These include:
- Weight loss
- Chronic diarrhoea
- Night sweats
- Skin problems
- Recurrent infections
- Serious, life-threatening illnesses
Today it's more akin to a long-term condition than a certain death sentence and the number of new infections are declining in most parts of the world.
Earlier this year health secretary Matt Hancock promised by 2030 there would be no new cases of HIV in England.
Co senior investigator Dr Howard Gendelman, of Nebraska University, who developed LASER ART, said: "This achievement could not have been possible without an extraordinary team effort that included virologists, immunologists, molecular biologists, pharmacologists, and pharmaceutical experts.
"Only by pooling our resources together were we able to make this groundbreaking discovery."
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In previous work, Dr Khalili's team used CRISPR-Cas9 technology to develop a novel gene editing and gene therapy delivery system aimed at removing HIV DNA from genomes harbouring the virus.
In rats and mice, they showed that the gene editing system could effectively excise large fragments of HIV DNA from infected cells, significantly impacting viral gene expression.
Similar to ART, however, gene editing cannot completely eliminate HIV on its own. The researchers now believed they have solved the problem.
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