Gene Editing Can Eliminate HIV From Cell Culture, Researchers Claim
Researchers claim they can eliminate HIV from lab-cultured cells using CRISPR-Cas9 gene editing.
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This article is based on research findings that are yet to be peer-reviewed. Results are therefore regarded as preliminary and should be interpreted as such. Find out about the role of the peer review process in research here. For further information, please contact the cited source.
The genome editing tool CRISPR-Cas9 can eliminate HIV viruses from lab-cultured cells, according to not-yet peer-reviewed research to be presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Barcelona.
Though the researchers stress the findings remain “proof-of-concept” and far away from potential clinical use, the work could bring the search for an HIV cure one step closer.
Proof-of-concept in cell culture
The researchers behind the discovery of CRISPR-Cas9 genome editing received the 2020 Nobel Prize in Chemistry for their groundbreaking discovery.
The editing tool acts like a pair of molecular scissors to selectively cut out and modify pieces of an organism’s genetic code. It can be used for applications such as deleting unwanted or faulty genes and introducing new genetic material in its place.
There are already some CRISPR-based therapies in development – the first was approved by the US Food and Drug Administration (FDA) in 2023 to treat sickle cell disease.
The scientists behind the research to be presented at ECCMID applied this technology to target HIV. The virus infects immune cells such as T cells, macrophages and dendritic cells.
Infection with HIV is currently treatable with lifelong antiviral therapy to reduce viral load to undetectable levels, but it is not curable. This is due to the virus’ ability to integrate its genome into its host’s DNA, preventing it from being eliminated. Additionally, if antiviral treatment is stopped, HIV can rebound from reservoirs of other infected cells.
“Our aim is to develop a robust and safe combinatorial CRISPR-Cas regimen, striving for an inclusive 'HIV cure for all' that can inactivate diverse HIV strains across various cellular contexts,” the researchers explained in a press release.
A long way from the clinic
The researchers adopted a broad-spectrum approach by using CRISPR to focus on two regions of the HIV genome that are conserved across all known strains of HIV.
However, they found that the size of the vehicle that transports the CRISPR-Cas9 reagents to the infected cells was too large and had to be downsized to make for easier transportation.
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Subscribe for FREEThey also tackled the problem of the cells that function as a reservoir for HIV when antiviral treatment is stopped. These “hidden” cells were targeted by focusing on two proteins – CD4 and CD32 found on the cell surface – to direct the delivery of the CRISPR gene editing machinery.
Several experts, who were not involved in the study, had their say on the reported findings.
“I would consider that, as the researchers note, this is a long way from the clinic,” said Prof. Simon Waddington, professor of gene therapy at University College London. “It is a long path from showing proof-of-concept in cells in a dish to applying this in the clinic.”
Dr. James Dixon, associate professor of stem cell and gene therapy technologies at the University of Nottingham, also stressed the importance of the need for these findings to undergo peer review: “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 an impact on those with HIV,” said Dixon.
“Our next steps involve optimizing the delivery route to target the majority of the HIV reservoir cells,” the researchers explained. “We will combine the CRISPR therapeutics and receptor-targeting reagents and move to preclinical models to study in detail the efficacy and safety aspects of a combined cure strategy. This will be instrumental to achieving preferential CRISPR-Cas delivery to the reservoir cells and avoiding delivery into non-reservoir cells.”
References:
Fan M, Kroon PZ, Berkhout B, Herrera Carrillo E. Impact of CRISPR-Cas gene cassettes on the packaging efficiency and transduction titer of lentiviral vectors. Poster presented at: European Congress of Clinical Microbiology and Infectious Diseases; April 2024; Barcelona, Spain.
Yu Z, Bao Y, Andrade Dos Ramos ZS, et al. CRISPR-Cas therapy towards a cure for HIV/AIDS. Oral presentation at: European Congress of Clinical Microbiology and Infectious Diseases; April 2024; Barcelona, Spain.
Bao Y, Yu Z, Berkhout B, Herrera-Carrillo E. Extinction of all infectious HIV in cell culture by the CRISPR-cjCas9 system. Poster presented at: European Congress of Clinical Microbiology and Infectious Diseases; April 2024; Barcelona, Spain.
Yu Z, Bao Y, Alcalá Lalinde A, Berkhout B, Herrera Carrillo E. Elimination of infectious HIV DNA by CRISPR–saCas9. Poster presented at: European Congress of Clinical Microbiology and Infectious Diseases; April 2024; Barcelona, Spain.
