Tuesday February 18, 2020

CRISPR Gene Editing can Cause Risky Collateral DNA Damage: Study

The work has implications for how CRISPR/Cas9 is used therapeutically and is likely to re-spark researchers' interest in finding alternatives to the standard CRISPR/Cas9 method for gene editing

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genes
Gene triggering antibiotic reaction risk identified. Pixabay

The much celebrated CRISPR/Cas9 gene editing technique can cause greater genetic damage in cells than was previously thought, scientists have warned.

CRISPR/Cas9 is a type of molecular scissor technology that can alter sections of DNA in cells by cutting at specific points and introducing changes at that location.

Besides extensive use in scientific research, CRISPR/Cas9 has also been seen as a promising way to create potential genome editing treatments for diseases such as HIV, cancer or sickle cell disease.

But the new research, reported in the journal Nature Biotechnology, revealed that CRISPR/Cas9 frequently caused extensive mutations, though at a distance from the target site.

Many of the cells, in both mice and humans, had large genetic rearrangements such as DNA deletions and insertions.

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CRISPR/Cas9 frequently caused extensive mutations, though at a distance from the target site.. Pixabay

These could lead to important genes being switched on or off, which could have major implications for CRISPR/Cas9 use in therapies.

In addition, some of these changes were too far away from the target site to be seen with standard genotyping methods, the researchers said.

“This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells, and we found that changes in the DNA have been seriously underestimated before now,” said Allan Bradley, Professor at the Wellcome Sanger Institute in London.

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“It is important that anyone thinking of using this technology for gene therapy proceeds with caution, and looks very carefully to check for possible harmful effects,” Bradley added

The work has implications for how CRISPR/Cas9 is used therapeutically and is likely to re-spark researchers’ interest in finding alternatives to the standard CRISPR/Cas9 method for gene editing.

“While it is not known if genomic sites in other cell lines will be affected in the same way, this study shows that further research and specific testing is needed before CRISPR/Cas9 is used clinically,” the researchers said. (IANS)

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Males Have Higher Risk of Suffering from Cancer: Study

Researchers explain why cancer risk is higher in males

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Cancer
DNA differences between men and women may explain why cancer risk is higher in males. Pixabay

DNA differences between men and women may explain why cancer risk is higher in males, according to a new study.

In findings published in the Journal of the National Cancer Institute, researchers have reported that loss of function in certain genes of the sex-determining Y chromosome, which is present only in men, may cause them to have an elevated risk for cancer.

Using data from 9,000 individuals, the researchers studied Y-chromosome gene function in patients with various types of cancer. The findings showed that cancer risk increases with loss of function of six key Y-chromosome genes in various types of cells.

“Recent studies have shown that complete loss of the Y chromosome, which is essential to foetal sex differentiation, occurs, with aging, in the cells of some men,” said study author Juan Ramon Gonzalez from Barcelona Institute for Global Health in Spain.

Cancer DNA
Suppression of the Y chromosome can occur as a result of loss of function in the chromosome. Pixabay

“Although the loss of the Y chromosome has previously been associated with higher incidence of cancer, the causes of this association are poorly understood,” Gonzalez added.

These six Y-chromosome genes are involved in cell-cycle regulation, the failure of which can lead to tumour development.

According to the study, understanding the biological differences between men and women in cancer is crucial for the development of personalised lines of treatment and prevention.

“Men are not only at higher risk of cancer than women, they also face a worse prognosis. In fact, these differences partially account for the lower life expectancy of men,” Gonzalez added.

According to the researchers, although men may be more exposed to carcinogens due to the type of work they do and at higher risk because they are less likely to consult a doctor, the study has shown that there are also biological factors that increase cancer risk among men.

“In fact, it seems that one of these factors can be found in the Y chromosome, the very essence of maleness,” said study lead author Alejandro Caceres.

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Suppression of the Y chromosome can occur as a result of loss of function in the chromosome, which would explain previous findings, or as a result of other mechanisms mediated by the chemical (epigenetic) inactivation of the same regions, the research said.

“Certain environmental exposures, for example to tobacco or other harmful substances, could affect chromosome function and lead to epigenetic modifications,” Gonzalez said. (IANS)