Why may CRISPR therapy promote cancers?

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Why may CRISPR therapy promote cancers?

Potential danger: CRISPR therapy may promote cancers, study shows.

Tel Aviv University researchers recently warned: “CRISPR genome editing methods are very effective, but not necessarily safe.

Sometimes the chromosomes that are cleaved are not restored and the stability of the genome is compromised – which may promote cancer in the long run. occur.”

According to recent research from Tel Aviv University, the use of CRISPR therapy — a new, Nobel Prize-winning technology that requires the cleavage and editing of DNA to treat diseases including cancer, liver and intestinal diseases, and genetic syndromes — will bring harm.

The researchers looked at how the technique affected T cells, the white blood cells in the immune system, and found that up to 10 percent of the treated cells lost their genetic material.

They explain that this loss can lead to instability in the genome, which can lead to cancer.

Dr. Adi Barzel of Tel Aviv University’s Wise School of Life Sciences and Dotan Center for Advanced Therapy led the study, a collaboration between Tel Aviv Sulaski Medical Center (Ichilov) and Tel Aviv University, with TAU Faculty of Medicine and Edmond J. . Dr. Asaf Madi and Dr. Uri Ben-David of the Safra Center for Bioinformatics.

The research was recently published in the prestigious scientific journal Nature Biotechnology .

Why may CRISPR therapy promote cancers?

CRISPR is a revolutionary DNA editing technology that cleaves DNA sequences at specific locations to eliminate unwanted segments or repair or introduce beneficial segments.

Developed about a decade ago, this approach has proven quite successful in treating a variety of diseases, including cancer, liver disease, genetic syndromes, and more.

The first licensed clinical study using CRISPR took place at the University of Pennsylvania in 2020, when researchers applied the technology to T cells — the white blood cells of the immune system.

Using T cells from a donor, the scientists created an engineered receptor that targets cancer cells, while using CRISPR to disrupt the genes encoding the original receptors that would otherwise prompt the T cells to attack cells in the recipient.

In this study, the researchers sought to investigate whether the potential benefits of CRISPR therapy might be outweighed by the risks posed by the cleavage itself, assuming that broken DNA doesn’t always recover.

Dr Ben-David and his research assistant Eli Reuveni explained: “The genome in our cells is often broken due to natural causes, but usually it repairs itself without causing harm. However, sometimes a chromosome still fails to bounce back, and a large Segments, or even entire chromosomes, can be lost. This chromosomal disruption can destabilize the genome, and we often see this in cancer cells. Therefore, CRISPR therapy, which is the deliberate cleavage of DNA as a means of treating cancer, in In extreme cases, it may actually promote malignancy.”

To examine the extent of the potential damage, the researchers repeated the 2020 Pennsylvania experiment by lysing the genomes of T cells on the exact same locations — chromosomes 2, 7 and 14 (23 pairs of chromosomes in the human genome).

Using a state-of-the-art technique called single-cell RNA sequencing, they analyzed each cell individually and measured the expression levels of each chromosome in each cell.

In this way, significant loss of genetic material was detected in some cells. For example, when chromosome 14 is cleaved, about 5% of cells show little or no expression of this chromosome.

When all chromosomes were cut at the same time, damage increased, with 9%, 10%, and 3% of cells failing to repair the breaks on chromosomes 14, 7, and 2, respectively.

However, the three chromosomes did differ in the degree of damage suffered.

Dr Madi and his student Ella Goldschmidt explained: “Single-cell RNA sequencing and computational analysis allowed us to obtain very precise results. We found that the difference in damage was due to the exact location of the cleavage on each of the three chromosomes. Overall, our findings show that more than 9 percent of T cells gene-edited with CRISPR technology have lost significant amounts of genetic material. This loss may lead to genomic instability, which may promote cancer.”

Based on their findings, the researchers caution that extreme caution should be exercised when using CRISPR therapies.

They also suggest alternative, less risky approaches for specific medical procedures and suggest further research into two potential solutions: reducing the production of damaged cells, or identifying damaged cells and using the material in patients remove it before.

Dr. Barzel and his doctoral student Alessio Nahmad concluded:

“Our intent in this study was to uncover the potential risks of using CRISPR therapeutics. We did so despite being aware of the enormous advantages of the technology.

In fact , among other research, we’ve developed CRISPR-based treatments, including a promising AIDS treatment. We’ve even started two companies — one using CRISPR and the other shunning the technology.

In other words In other words, we are advancing this highly efficient technology while drawing attention to its potential dangers.

It may seem like a contradiction, but as scientists we are quite proud of what we do because we believe this is the nature of science: We don’t ‘take sides’. We look at all sides of a problem, both positive and negative, and look for answers.”

Reference:

https://www.nature.com/articles/s41587-022-01377-0

Why may CRISPR therapy promote cancers?

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