Crispr technology rebounds from (now-retracted) unfavorable research results

Avatar By Lliane Hunter | 2 years ago

Last May, a small case study suggested that biotech’s big bet on Crispr technology might actually be quite dangerous, writes Megan Molteni for Wired.  Following the study, shares tanked for the gene-editing technique that made promises to snip away some of humanity’s most troubling diseases.  It was an overreaction, explains Molteni, scientists and journalists soon pointed out flaws in the paper that misconstrued cause and effect.

After nearly a year of unrelenting criticism, as well as failure to reproduce the results, the authors conceded that the skeptics might be right. Nature Methods, the journal that published the findings, recently retracted its results.  Crispr technology, however, still has hurdles to clear.  The retracted paper claimed that the gene-editing technology caused nearly 2,000 unexpected mutations in two mice that it cured of blindness.  Molteni believes that this is not necessarily a death-warrant for the technology as published data is limited.  Instead, more studies need to be completed.

Whether Crispr can safely be used in humans is still an open question.  But, developing trustworthy methods to detect off-target mutations has been a bit of a challenge and scientists, to-date, have only come up with about a half-dozen approaches.  The fastest and most economical is something called “targeted sequencing,” where researchers look for rogue snips in areas an algorithm suspects they might show up.  However, this method doesn’t detect mutations that pop up in unexpected places.

Biotech companies like Editas Medicine, Intellia Therapeutics, and Crispr Therapeutics are working on refining these methods of detection.  According to an Intellia spokesperson, the gene-editing firm is working with the US Food and Drug Administration and the National Institutes of Standards and Technology to help set specifications.

“We have developed a comprehensive workflow that uses a combination of both genome-wide assays and targeted sequencing to look for potential off-target mutations,” the company wrote in an email to Molteni.  “We always include appropriate controls in our experiments, such as sequencing of cells that are not edited.”

At Editas Medicine, scientists have developed a new way to evaluate Crispr edits called “Uni-Targeted Sequencing,” which can identify and quantify structural changes beyond cuts, deletions, and insertions.