Can a cure for AIDS, specifically HIV, come from new gene editing technology? A team of researchers from Amsterdam UMC in the Netherlands believes so and they have released the results of their research in which gene-editing technology to eliminate all traces of the virus from cells in a laboratory.
The researchers, led by Dr. Elena Herrera-Carrillo, used the CRISPR-Cas gene editing technology. This is a groundbreaking method in molecular biology that allows for precise alterations to the genomes of living organisms, which brought its inventors, Jennifer Doudna and Emmanuelle Charpentier, the Nobel Prize in Chemistry in 2020, and enables scientists to accurately target and modify specific segments of an organism’s DNA (genetic code).
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HIV, or Human Immunodeficiency Virus, is a virus that attacks the body’s immune system. HIV weakens the immune system by targeting and infecting CD4+ T cells, which are crucial for fighting off infections. If left untreated, HIV can progress to AIDS (Acquired Immunodeficiency Syndrome), a condition where the immune system is severely compromised.
While there is no cure for HIV, highly effective medications called antiretroviral therapy (ART) can suppress the virus to undetectable levels. This allows people with HIV to live long and healthy lives and prevents them from transmitting the virus to others through sex.
The CRISPR-Cas system, though often referred to as a single gene, is actually a much more intricate gene-editing tool. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein (Cas). It edits genes with high precision by cutting DNA at specific locations.
Imagine CRISPR-Cas as a pair of scissors (Cas protein) guided by a customized instruction sheet (CRISPR guide RNA) to precisely cut a specific piece of paper (DNA). Scientists adapted CRISPR-Cas from a natural defense system in bacteria that protects them from viruses.
“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,” said the researchers.
HIV can infect different types of cells and tissues in the body, each with its own unique environment and characteristics. The researchers are thus searching for a way to target HIV in all of these situations.
“We have developed an efficient combinatorial CRISPR-attack on the HIV virus in various cells and the locations where it can be hidden in reservoirs, and demonstrated that therapeutics can be specifically delivered to the cells of interest,” they added. “These findings represent a pivotal advancement towards designing a cure strategy.”
The authors emphasize that their work represents proof of concept, and will not become a cure for HIV tomorrow. They say, “Our next steps involve optimizing the delivery route to target the majority of the HIV reservoir cells. 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 achieve preferential CRISPR-Cas delivery to the reservoir cells and avoiding delivery into non-reservoir cells.
