Blogpost

by Dr. Sebastien Bertin-Maghit, PhD, faculty member at CSII.

CRISPR-Cas9. What a barbarian word. And yet so much hope for many diseases with no treatments so far.

CRISPR is short for Clustered Regularly Interspaced Short Palindromic Repeats. Still barbarian? OK, let\'s explain a bit what these repeats are.

To make it simple, CRISPR is a genome editing system developed by certain bacteria, allowing them to detect potential invaders\' genetic elements, from a virus, for instance, and, thanks to the CRISPR-Associated (Cas) nucleases, excise such elements. It would be the closest thing to a prokaryotic immune system, defending the cell from pathogens. The system is very good at (1) identifying specific sequences and (2) clearly cutting at the defined location.

A dream come true for geneticists and other biomedical scientists. Imagine that you now have a tool to cut DNA precisely where you want. Imagine having at your disposal molecular scissors to excise some sequences from your DNA. Such scissors pave the way to so many possibilities. One that comes to mind immediately is to remove genes from persistent infections\' pathogens. Think about HIV; the virus inserts its genetic material inside the patient\'s genome. It can remain dormant for months or years and suddenly reactivate out of the blue. Anti-HIV drugs consist today of antiretroviral molecules that will block the viral machinery when the virus wakes up, but they cannot cure the infection; patients bear the virus\'s genes forever. But with CRISPR, you could eventually remove the virus from the patient\'s body and cure the infection once and for all. Many clinical trials aiming at that goal are being conducted at the moment.

Because biologists were able to modify the Cas molecules, the system is now also able to modify genes, not only remove them. Real gene engineering is finally at reach, gene activation, gene silencing, gene modulation…

Gene engineering has so many potential uses; the CRISPR system has been used already to modify plants. With the system, the Genetically Modified Organisms (GMOs) can be engineered in an even cleaner way. Making crops resistant to pests, enabling the use of fewer harmful chemical pesticides, or making crops grow faster and bigger. Let\'s stop a minute on a recent example related to sustainability; in 2023, a team of scientists in the US used the CRISPR-Cas9 system to edit the genome of poplar trees to make wood with lower lignin content and with molecular ratios that favor easier fiber production. The wood grown from these modified trees required less water and less energy to get processed into pulp for paper manufacturing. In 2021, it was estimated that the paper-making industry had a global carbon footprint of 190 million tonnes. We see here that innovative biotechnologies are not only important in the health field but rather have applications in many fields and may address many of our modern societies\' challenges.

Going back to the Health sector, editing the human genome is opening new therapeutic solutions. Gene engineering may benefit many conditions: from blood diseases to metabolic disorders, from cardiovascular problems to immune/allergic dysfunctions. In late 2023, the first CRISPR-Cas9 derived treatment was first approved in the UK for β-thalassemia and sickle cell disease. The product developed by the Irish company Vertex Pharmaceuticals Limited was then approved by the US-FDA two weeks later and got a formal recommendation for approval by the European EMA on 15 December 2023, 4 years after getting its orphan designation.

Reprogramming cells that do not function properly can cure virtually anything. Thanks to the CRISPR system, this reprogramming is now possible and available. We may, however, need to act fast on the ethics side, to frame and regulate the use of that technology. Like many other technological tools, CRISPR may bring us the best, but also the worst if not used ethically. Reprogramming cells, modifying the human genome, such procedures mean altering what we intrinsically are and cannot be done without consequences.

To go further on that topic:

• Sharma G, Sharma AR, Bhattacharya M, Lee SS, Chakraborty C. CRISPR-Cas9: A Preclinical and Clinical Perspective for the Treatment of Human Diseases. Mol Ther. 2021 Feb 3;29(2):571-586. Epub 2020 Sep 20. DOI: 10.1016/j.ymthe.2020.09.028.
• Newsom S, Parameshwaran HP, Martin L, and Rajan R (2021) The CRISPR-Cas Mechanism for Adaptive Immunity and Alternate Bacterial Functions Fuels Diverse Biotechnologies. Front. Cell. Infect. Microbiol. 10:619763. DOI: 10.3389/fcimb.2020.619763
• Bhowmik, R., Chaubey, B. CRISPR/Cas9: a tool to eradicate HIV-1. AIDS Res Ther 19, 58 (2022). https://doi.org/10.1186/s12981-022-00483-y
• Daniel B. Sulis et al. Multiplex CRISPR editing of wood for sustainable fiber production. Science 381, 216-221(2023). DOI: 10.1126/science.add4514
• Michael Le Page. What is CRISPR. New Scientist, accessed online on 8 January 2024. https://www.newscientist.com/definition/what-is-crispr/

ALSO Read: The previous blogpost by the author: Reflections on 2023… And thoughts for 2024 and Beyond…