March 19, 2024

expert reaction to conference abstract about eliminating HIV in cell culture using CRISPR-Cas gene editing technology

Scientists react to a conference abstract about eliminating HIV in cell culture using CRISPR-Cas that is being presented at the European Congress of Clinical Microbiology and Infectious Diseases.

Prof Simon Waddington, Professor of Gene Therapy, University College London (UCL), said:

“I would consider that, as the researchers note, this is a long way from the clinic. I would actually say they are a very very long way from the clinic. It is a long path from showing proof of concept in cells in a dish to applying this in the clinic. 

“Along the path, these researchers will face several challenges: 1) being able to efficiently deliver their gene editing machinery to cells in a human being – and they may have to hit most or all infected cells – a huge task – technology is nowhere near this yet 2) they have to be able to show they can do this safely. Again a long journey.

“Given that antiretrovirals are showing such effectiveness (as far as I understand), they may face a tough challenge in presenting a good cost/benefit/risk balance.”

Dr James Dixon, Associate Professor – Stem Cell & Gene Therapy Technologies at the University of Nottingham:

“This is an interesting study in which gene-editing technology has been used to remove the permanent nature of how HIV inserts and retains its genome in that of patient cells. HIV inserts its genome (it converts itself from RNA to DNA) into infected cells, therefore it stays in the body for however long those cells remain, even if they are effectively treated by new anti-viral therapies, and indeed can remain as reservoirs for reinfection after treatment is stopped. Using CRISPR technology to snip out or deactivate the HIV genome is a well discussed but promising strategy, however the delivery of these systems remains a significant issue and much more work will be needed to demonstrate results in these cell assays can happen in an entire body for a future therapy. As this is not peer reviewed it will be important to assess the specific data that confirms the findings and there will be much more development needed before this could have impact on those with HIV.”

Dr Alena Pance, Senior Lecturer in Genetics, University of Hertfordshire, said:

“This advance seems to have enormous potential as a novel approach for HIV therapy. However, it is not straightforward to evaluate this from the information given because there are limited technical details. Mainly, the abstract mentions two therapeutic approaches, one in which the virus is inactivated, but it is unclear what this means, inactivating the capacity of the virus to re-start its replicative cycle or disrupting critical genes for example. The second is using 2 gRNAs to excise the virus from the genomes of the infected cells completely, which is a very attractive option, but it would be good to know whether the virus is also inactivated at the same time and what happens on a longer-term follow up.

“The work presented does bring hope with yet another application of CRISPR/Cas9 technology not just for HIV but also potentially for other viral diseases that are major world-wide public health problems.”

Dr Jonathan Stoye, Senior Group Leader and Head of the Retrovirus-Host Interactions Laboratory, Francis Crick Institute, said:

“The idea of a functional cure for AIDS using CRISPR-Cas9 technology to purge the body of HIV-1 has enormous appeal.  Many groups are working in this area and at least one company, Excision BioTherapeutics, has already initiated clinical trials of a small number of HIV-1 infected individuals.  However, the challenge of removing HIV genomes from all the cells that make up the long-lived viral reservoirs in such people is extremely challenging.  In addition, off-target effects of the treatment, with possible long-term side effects, remain a concern. It therefore seems likely that many years will elapse before any such CRISPR-based therapy becomes routine even assuming that it can be shown to be effective.”

Dr Andrew Freedman, Reader in Infectious Diseases, Consultant in Infectious Diseases and Vaccine Clinical Trials, Cardiff University, said:

“Although current antiretroviral drug treatment (ART) is highly effective and generally well tolerated, it has to be taken lifelong.  The search for a cure for HIV which would enable patients to discontinue ART has been ongoing for many years.  This requires eradicating the so called latent HIV reservoir of dormant T cells harbouring the virus.  Attempts to date have not managed to achieve this, other than the very few, well publicised cases of patients being cured by bone marrow transplantation.”

“This new study has employed the technique of gene editing to inactivate part of the HIV genome in infected T cells in the laboratory.  As the authors point out, this work represents a successful proof of concept, but the challenge will be to translate this into a treatment which can achieve the same result in HIV infected patients.  This is not straightforward and would likely take many years of further research.  In the meantime, the focus needs to remain on prompt diagnosis of HIV infection and initiation of antiretroviral therapy.”

Conference abstract title: ‘HIV/AIDS (incl diagnostics & epidemiology, anti-retroviral drugs, vaccines, treatment & susceptibility/resistance)’ by Z. Yu et al.

This was under embargo until 2301H UK time Tuesday 19 March.

There is no full paper and the conference abstract is not peer reviewed.

Declared interests

Dr Pance: No conflicts on interest to declare.

Dr Stoye: No conflicts of interest to declare.

Prof Freedman: No conflicts of interest to declare.

For all other experts, no reply to our request for DOIs was received.