A study by Wellcome Sanger Institute researchers showed CRISPR-Cas9 (CRISPR-associated protein 9) produced no unexpected off-target edits in mice, countering a 2017 report of high off-target activity and confirming doubts about that study’s results from CRISPR experts. The new study, not yet peer-reviewed, was published on the preprint server bioRxiv.
In a letter published in Nature Methods last year, researchers from Stanford University, Columbia University and the University of Iowa said the CRISPR-Cas9 gene editing technique led to unexpected off-target mutations in mice, causing shares of gene editing companies to sink (see BioCentury Innovations, June 1, 2017).
The letter drew criticism from gene editing companies and experts, who proposed alternative explanations for the high level of genetic variants detected in the mice. In a response to the letter, executives at Editas Medicine Inc. (NASDAQ:EDIT) and academic CRISPR expert and company adviser George Church reanalyzed the data and concluded natural genetic variation rather than the CRISPR treatment was the likely explanation (see BioCentury Extra, June 22, 2017).
In the new study, the Sanger Institute group identified use of strain-matched, but not pedigree-matched animals as the previous study design’s flaw.
The team used whole-genome sequencing on mouse embryos from four sets of parents to show that the number of off-target single-nucleotide variations and insertions and deletions (indels) in embryos treated with CRISPR-Cas9 using guide RNAs targeting the pigmentation gene tyrosinase (TYR; OCA1) matched the expected background rate for de novo mutations. The number of off-target variants did increase when comparing variations between related embryos and unrelated embryos, suggesting the variants can be attributed to natural genetic differences and not the treatment.
On Monday, CRISPR Therapeutics AG (NASDAQ:CRSP) added $2.49 to $37.37 and Intellia Therapeutics Inc. (NASDAQ:NTLA) gained $1 to $24.48, while Editas was off $0.84 to $32.85.