CRISPR gene tool can cause unintended flaws in genome

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New York, May 30 (IANS) The CRISPR-Cas9 gene-editing technology can introduce hundreds of unintended mutations into the genome, warns a new study.

“We feel it’s critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome,” said co-author Stephen Tsang, Associate Professor at Columbia University Medical Centre in the US.

CRISPR-Cas9 editing technology — by virtue of its speed and unprecedented precision — has been a boon for scientists trying to understand the role of genes in disease.

The technique has also raised hope for more powerful gene therapies that can delete or repair flawed genes, not just add new genes.

The first clinical trial to deploy CRISPR is now underway in China, and a US trial is slated to start next year.

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But even though CRISPR can precisely target specific stretches of DNA, it sometimes hits other parts of the genome.

Most studies that search for these off-target mutations use computer algorithms to identify areas most likely to be affected and then examine those areas for deletions and insertions.

“These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals,” co-author Alexander Bassuk, Professor at the University of Iowa, said.

In the new study, published in the journal Nature Methods, the researchers sequenced the entire genome of mice that had undergone CRISPR gene editing in the team’s previous study and looked for all mutations, including those that only altered a single nucleotide.

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The researchers determined that CRISPR had successfully corrected a gene that causes blindness, but they also found that the genomes of two independent gene therapy recipients had sustained more than 1,500 single-nucleotide mutations and more than 100 larger deletions and insertions.

None of these DNA mutations were predicted by computer algorithms that are widely used by researchers to look for off-target effects.

“We’re still upbeat about CRISPR,” co-author of the study Vinit Mahajan, Associate Professor at Stanford University, said.

“We’re physicians, and we know that every new therapy has some potential side effects – but we need to be aware of what they are,” Mahajan added.



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