Home » Cut and sew with DNA? All the risks of Crispr

Cut and sew with DNA? All the risks of Crispr

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Cut and sew with DNA?  All the risks of Crispr

Crispr-Cas9, the DNA cut-and-sew technique, is an efficient method of engineering cells. It promises great things, from new cancer treatments to those for rare diseases like thalassemia. But perhaps it is less sure than we think. This, in a nutshell, is the conclusion reached by a team of researchers from the University of Tel Aviv.

As they explain in the study published in the journal Nature Biotechnology, Israeli scientists replicated the experiments that led to the first U.S. clinical trial of genetically engineered immune system cells with Crispr to fight certain cancers in 2020, and found that up to 9-10% of cells are compromised. A condition that could also promote cancer.

The first experiment

The tenth birthday of the technique that revolutionized genetic engineering, Crispr-Cas9, has just passed. Considered very effective, efficient, precise and easy to use compared to other DNA modification systems, Crispr-Cas9 in 2020 was awarded the Nobel Prize in Chemistry to Jennifer Doudna e Emmanuelle Charpentier. Over the years it has found countless applications, including in the clinic.

Just in 2020, the first human experimentation of cells modified with Crispr-Cas9 was conducted in the United States, by a team of the University of Pennsylvania, coordinated by Carl Juneone of the world‘s leading experts in immunotherapy (i.e. the strategy that enhances the immune system to fight cancer), pioneer of CAR-T cells.

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Research on tumors

In the article published by Science, the US researchers showed the approach used to modify the T lymphocytes of some patients with treatment-refractory advanced myeloma and metastatic sarcoma in the laboratory. Crispr-Cas9 destroyed three genes and introduced a transgene – all to make T lymphocytes more efficient at recognizing and destroying cancer cells.

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The results were encouraging: the engineered cells had survived in the three patients for a long time and had kept the tumors at bay, although they had not completely eliminated them. Crispr-Cas9, according to June and colleagues, had made point changes on the affected chromosomes in most cases, even if some errors (such as some chromosomal translocations) had been detected.

Is Crispr-Cas9 Really Safe?

To establish the actual safety of this genetic engineering approach, the Israeli team took up the experiments of US colleagues, replicated them and analyzed, through single-cell RNA sequencing, the genome integrity of thousands. of cells. Scientists concluded that 9-10% of treated cells lose a significant amount of genetic material.

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Sometimes the chromosomes that are cut do not fix and the genetic material is compromised – a condition that also occurs in some types of cancer. “Therefore, Crispr therapy, in which DNA is intentionally cleaved as a means of treating cancer, could, in extreme scenarios, actually promote malignant tumors,” he explains. Uri Ben-Davidamong the authors of the study.

The call for caution

“Our intention was to shed light on the potential risks in the use of Crispr therapies – he adds Adi Barzel, research coordinator -. We did it even though we are aware of the substantial advantages of this technology “.

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In short, it is necessary to pay more attention, and to deepen the research on methods that could improve the safety of therapies that use Crispr, for example improving the technique to reduce the percentage of damaged cells or identify the compromised cells and remove them before the material is administered. to the patient.

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