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CRISPR can't cut it against HIV

11 April 2016

By James Brooks

Appeared in BioNews 846

Scientists testing whether the CRISPR genome-editing technique could effectively kill HIV in infected cells have found that, while the approach works in most cases, it can also cement the virus's presence.

The study appeared just one month after a separate team published research in which CRISPR had been eliminated from cells taken from AIDS patients (see BioNews 845). Researchers from both teams have said that the current study illustrates that there are obstacles in the way of a CRISPR-based therapy for HIV, but these may not be insurmountable.

In the study, scientists used CRISPR to cut out a section of DNA in human cells that is introduced by the HIV when an infection occurs. The genetic code that HIV integrates into the human genome makes cells produce more HIV particles.

In many cases this approach worked – once the viral DNA was removed, the cell automatically patched the section of cut DNA with a different genetic code and the cell no longer produced HIV particles.

But in others the DNA 'patch' actually made the virus stronger, for example by speeding up virus replication. Furthermore, the patched section of DNA was no longer recognisable to the CRISPR system, meaning that any attempt to treat resistant cells for a second time would not work.

'On the one hand, CRISPR inhibits HIV, but on the other, it helps the virus to escape and survive,' senior study author Dr Chen Liang, of McGill University in Montreal, Canada, told New Scientist. 'The surprise is that the resistance mutations are not the products of error-prone viral DNA copying, but rather are created by the cell's own repair machinery.'

However, Dr Liang's team is not the first to observe HIV's resistance to CRISPR. In February, a team from the University of Amsterdam published similar results.

Dr Liang now says that researchers in the field should concentrate on using genome-modifying techniques that could circumvent HIV's resistance. These might include using enzymes other than Cas9 – which is most often used with CRISPR – to cut out viral DNA at different sites, or bombarding cells with CRISPR to cut out viral DNA at several sites instead of just one.

Other researchers in the field are less confident. Professor Bryan Cullen, a virologist at Duke University in the USA, also uses CRISPR as a research tool but was not involved in the current study. He told Nature News that any therapeutic use of CRISPR would require genetically modifying a substantial number of a patients' immune cells. Given the difficulties of such an approach, and the fact that it is becoming easier to manage most HIV infections with cocktails of antiretroviral drugs, Professor Cullen said that he considered CRISPR-based treatments for HIV to be 'pie in the sky'.

Dr Liang's study was published in Cell Reports.

Cell Reports | 07 April 2016
Eurekalert (press release) | 07 April 2016
New Scientist | 07 April 2016
Nature | 07 April 2016
The Scientist | 07 April 2016


08 May 2017 - by Emma Laycock 
US scientists have used CRISPR gene-editing to remove HIV DNA from the genomes of living animals, eliminating further infection.
24 April 2017 - by Jennifer Willows and Annabel Slater 
A new highly sensitive diagnostic system for diseases has been adapted from CRISPR...
17 October 2016 - by Sarah Gregory 
Researchers have used the CRISPR/Cas9 genome-editing technique to correct the mutation that causes sickle-cell anaemia...
12 September 2016 - by Dr Özge Özkaya 
Scientists from China have managed to shrink the size of tumours in mice using CRISPR/Cas9 genome-editing technology...
13 June 2016 - by Rhys Baker 
Over just 30 minutes Fergus Walsh has a lot of ground to cover here without even touching on the ethical debate. Yet, while gene editing may have 'just been made simple', how we respond to these stunning advances is anything but...

11 April 2016 - by Ayala Ochert 
A second team in China report that they have created genetically modified human embryos, in an attempt to make them resistant to HIV, using the genome-editing technique CRISPR/Cas9...
04 April 2016 - by Dr Lanay Griessner 
Scientists have used the CRISPR genome-editing technique to remove HIV from the DNA of infected T cells and prevent reinfection...
07 March 2016 - by Kirsty Oswald 
Researchers have found that mimiviruses, a class of giant viruses, have an immune system reminiscent of the CRISPR system used by bacteria to evade infection...
11 January 2016 - by Paul Waldron 
Researchers have improved the genome-editing technique CRISPR/Cas9, reducing errors to nearly undetectable levels, according to a new study...
03 August 2015 - by Lubna Ahmed 
Researchers have successfully used the technique CRISPR/Cas 9 to cut and paste genes into T-cells of the immune system...

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