CRISPR may not be as precise as early studies suggest

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A popular gene-editing technique may unintentionally delete and rearrange DNA bases, according to a new study published in Nature Biotechnology.

The study involves the use of CRISPR-Cas9, a system many scientists consider one of the most precise gene-editing techniques used in research today. CRISPR-Cas9 enables scientists to add, remove or replace pieces of an organism's DNA by creating modified RNA segments that exploit select enzymes. This year, the first U.S. clinical trial to treat humans with the CRISPR gene-editing technique began patient recruitment.

However, a team of researchers from the Wellcome Sanger Institute in England is arguing CRISPR-Cas9 isn't as precise as initial research would suggest. The researchers noted early studies into CRISPR-Cas9 focused on genetic alterations that were "limited to the immediate vicinity of the target site … leading to the conclusion that CRISPR–Cas9 was reasonably specific."

For their study, the researchers used long-read sequencing and long-range genotyping to investigate how cutting DNA with CRISPR-Cas9 affects other areas of a cell's DNA. Their experiment — conducted in select cells from mice and humans — found CRISPR-Cas9 caused unexpected "large deletions" and "complex genomic rearrangements" in the DNA.

In the conclusion to their study, the researchers characterized their observations as "genomic damage" that "may have pathogenic consequences." Some deletions can silence genes that should be active, and vice versa — such as activating a gene that causes cancer, STAT reports.

The collateral DNA damage from CRISPR-Cas9 gene editing has been "seriously underestimated," lead author Allan Bradley, PhD, told STAT. "This should be a wake-up call."

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