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expert reaction to study looking at combination therapy involving CRISPR to treat HIV in mice

Researchers, publishing in Nature Communications, have reported the use of CRISPR based gene editing technology in combination with antiviral drugs to treat HIV in mice. 

 

Dr Jonathan Stoye, Group Leader, Retrovirus-Host Interactions Laboratory, The Francis Crick Institute, said:

“This is a tremendously exciting paper offering a vision of a potential path to permanent cure to AIDS in the future.  By combining anti-retroviral therapy to repress HIV-1 growth with gene editing techniques to remove the hidden retrovirus reservoir, the authors have convincingly demonstrated the complete elimination of HIV-1 from about one third of experimentally infected mice.  By contrast, in humans, HIV-1 has so far only been removed from two AIDS patients out of more than 35 million infected individuals and using far riskier procedures.

“However, this paper is just a start of a long road.  A number of important questions remain to be answered including:

“(i) Why did the procedure followed not work in two thirds of the mice?

“(ii) Are humanized mice really good models for HIV-1 infection of humans?

“(iii) Will there be unanticipated side effects of the gene editing procedure when applied to humans?

“(iv) Can one effectively scale up the procedure from mouse to human given that missing only a few viral targets will allow the virus to rebound?”

 

Prof Paul Freemont, Co-Director of the Centre for Synthetic Biology and Innovation, Imperial College London, said:

“This is an exciting study showing that it might be possible to use a chemical and genetic editing therapy in combination to eliminate HIV permanently from infected cells.  HIV is very clever in that it embeds its own genetic code into cells which when activated can make more virus, and so methods to both kill active viruses and also eliminate HIV genetic code in infected cells are needed.  However the number of mice used in the study is small and further trials will be needed to confirm this initial but exciting proof-of-concept study.  However, it is still an open question as to whether such an approach would work in humans, particularly off-target effects.”

 

* ‘Sequential LASER ART and CRISPR treatments eliminate HIV-1 in a subset of infected humanized mice’ by Prasanta K. Dash et al. was published in Nature Communications at 16:00 UK time on Tuesday 2 July 2019.

DOI: 10.1038/s41467-019-10366-y

 

Declared interests

Prof Paul Freemont: “I have no conflicting interests.”

None others received.

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