HIV 'cut out' of human genome

Research has shown that it may be possible to 'cut' the viral DNA out of cells infected by HIV using genetic editing techniques, removing its ability to replicate. This may allow for HIV to be extracted from the body's DNA where it can lay dormant following anti-viral treatment. 

Current HIV therapies can reduce the amount of virus produced in an infected person, holding AIDS at bay, giving patients a chance at a normal length of life. However, even if drugs are successful in reducing the amount of virus in a patient's blood to undetectable levels there can still be hidden 'reservoirs' of virus in other tissues.

HIV permanently inserts its own genome into the DNA of the cells that it infects. This allows the virus to hide in long-lived cells, potentially reactivating years later, which is why current drugs only treat but do not cure the infection.

The research, published in PNAS, explores a way to cut the virus' DNA out of the infected cells' DNA. The authors used a technology that cuts DNA at specific, bespoke sequences. Targeted against the ends of the inserted HIV DNA, this can result in the viral genomes being snipped out, physically removing the ability of that cell to produce more virus, before repair enzymes in the cell stitch the cut chromosomes back together.

The process borrows a technique that evolved in some bacteria to protect them from viruses that try to insert into their bacterial genomes. It is a two-part defence system, involving a short sequence of RNA and an enzyme called Cas9. A guide RNA is produced to specifically recognise the ends of the HIV genome and Cas9 cuts it out.

The researchers used this technique to cut the HIV DNA out of the genome of several different cell types representative of those infected in people, successfully removing even multiple copies of the virus from the human chromosomes. More importantly, the presence of the guide RNA and Cas9 in a cell prevented that cell from becoming infected, immunising against future infection.

'We are working on a number of strategies so we can take the construct into preclinical studies', said lead author Professor Kamel Khalili, from Temple University, USA. 'We want to eradicate every single copy of HIV-1 from the patient. That will cure AIDS. I think this technology is the way we can do it'.

This is not the first time that such genetic-editing techniques have been deployed to fight HIV. The research in this paper builds on that published by a Japanese group last year by increasing efficiency and decreasing the chance of toxicity associated with the treatment. Other tactics involve trying to edit the human genome to make it harder for HIV to infect cells, such as efforts published earlier this year to modify a receptor that HIV needs to get in to cells (see BioNews 758).

Even more recently, results presented at the AIDS 2014 conference last week showed researchers using drugs to reactivate 'silent' HIV in patients', which might expose infected cells making them more likely to be removed by the immune system.

While the authors of this paper performed a number of tests to show that the presence of the Cas9 wasn't cutting or mutating human DNA at other sites, the removal of HIV (and prevention of future infection) was only seen in the portion of cells that both took up and correctly expressed the relevant DNA coding.

Moreover, getting DNA into cells in culture is relatively simple; getting it into the rare cells in the human body that might harbour HIV genomes will present the major challenge before the technology can become clinically useful.