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Will a New Technique to Treat HIV Make the Cut?

Researchers at the University of Amsterdam in the Netherlands recently reported a new method to directly “cut” the genetic material of human immunodeficiency virus (HIV) out of infected cells. In a statement released ahead of the European Congress of Clinical Microbiology and Infectious Diseases — where this work is due to be presented in April — Dr Elena Herrera Carrillo, spearheading the research, believes “these findings represent a pivotal advancement towards designing a cure strategy.”

 

The new method involves using the ground-breaking CRISPR-Cas gene editing system. Pioneered by Jennifer Doudna and Emmanuelle Charpentier, the development and application of this genetic engineering technique has received a lot of attention in recent years and famously won the 2020 Nobel Prize in Chemistry. CRISPR-Cas acts like a pair of scissors at the DNA level, nicking specific genetic material so that it can be removed or replaced. This is particularly relevant in the case of HIV, as the virus infects cells which make up our immune system — such as white blood cells and T cells — by inserting its genetic material into our own.




Image: Unsplash

 

Once locked inside strands of DNA, the HIV genome (the entirety of its DNA) is indistinguishable from that of the host, hiding in plain sight from the immune system. Because of this, natural DNA replication within our cells inadvertently duplicates the HIV genome as well. This results in the production of more virus particles which kill and escape from their original host cell, infiltrating the bloodstream and marching on to invade other cell types.

 

HIV can go undetected in the body for several years, all the while assassinating immune cells until their numbers are as low as 200 per microlitre of blood. This is the typical marker that permits the diagnosis of acquired immunodeficiency syndrome (AIDS) and represents a dramatic reduction from the typical 500-1500 cells found per microlitre of blood in an HIV-negative person.

 

HIV originated in chimpanzees and was likely to have been transmitted to humans in the late 1800s. By the 1980s, HIV was widespread in the US. The number of known deaths per year peaked at 48,371 in 1995. According to the World Health Organisation (WHO), since the beginning of the epidemic around 40.4 million people have died from AIDS.

 

With increased testing, diagnosis, and anti-retroviral treatment, the number of people dying from AIDS has decreased since then. Although mortality rates have fallen and people with HIV can lead relatively healthy lives without progression to AIDS, those from low- and middle-income countries are more susceptible to the disease than people from economically advantaged regions. Despite the introduction of pre-exposure prophylaxis (PrEP) — a medication used to prevent HIV infection — this treatment is only just starting to be made available in poorer countries. Even though the WHO has made a commitment to end AIDS by 2030, they have stated that infection and mortality rates are dropping too slowly to meet this target.    

 

Although this work from the Netherlands represents a new milestone in the treatment of HIV and AIDS, further research must be done to evaluate its potential therapeutic effects. While the “cutting” method may work in small clusters of cells under controlled laboratory conditions, how it operates within the natural complexity of the human body is yet to be determined. HIV can trickle through different cell types and tissues, feeding into discrete reservoirs of infection. If this treatment is to work, it must prioritise delivery to these HIV reservoirs, killing directly at the source. 


And yet, in the fight against HIV, the innovation provides an extra tool in the modern scientist’s lab-coat pocket: the CRISPR-Cas system, our trusty pair of genetic scissors, sharpened and ready.

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