30 May 2017

Be careful with genome editing!

The CRISPR gene editing method turned out to be the source of hundreds of unwanted mutations

Oleg Ovechkin, Rusbase

Scientists from the USA have discovered that the CRISPR-Cas9 genome editing method can lead to hundreds of unintended mutations, and popular algorithms for predicting the effect of CRISPR on the body give erroneous results. This is reported by the authors of the study.

The CRISPR technique was borrowed by scientists from the immune system of bacteria. Since 2013, when CRISPR was adapted as a technology, the method has gained great popularity among the scientific community due to successful experiments with the point removal of genes responsible for genetic diseases. In the future, CRISPR can completely cure diseases like HIV and introduce the desired genes into the body.

To predict the effect of CRISPR on genes, scientists usually use computer algorithms. As a group of researchers from several American universities found out, these programs can make mistakes and "skip" hundreds of side mutations in the genome.

As part of their work , the researchers sequenced (learned the sequence of genes) the complete genome of two mice that independently underwent CRISPR therapy. The results of the initial study were confirmed – the technique really allowed rodents to get rid of the gene that led to blindness.

However, together with the removal of one unwanted gene, CRISPR led to mutations in 1,500 nucleotides and more than a hundred "large" gene deletions and insertions in these mice, the scientists found. The algorithms were unable to predict any of these mutations.

"These predictive algorithms seem to be effective when CRISPR is applied to cells or tissues in vitro, but scientists do not use full genome sequencing to find all the side effects for living organisms," said Alexander Bassuk, one of the co–authors of the study from the University of Iowa.

According to Bassuk, the scientists did not find a pronounced negative effect of unintended mutations on the mice studied. However, due to the potential that a random mutation of even a single nucleotide can carry, the researchers recommend checking the side effects of CRISPR more carefully.

"We hope that the results of our study will serve as an incentive for scientists to use full genome sequencing to identify all the side effects of CRISPR and investigate safer and more accurate methods of editing [genes]," said Stephen Tsan, another co–author of the work from Columbia University.

The full text of the scientific paper “Unexpected mutations after CRISPR-Cas9 editing in vivo" was published in the journal Nature Methods, but at the time of publication of the note, the article was not yet available online.

Portal "Eternal youth" http://vechnayamolodost.ru  30.05.2017


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