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New Rules Takes the Guesswork out of Human Gene Editing

New Rules Takes the Guesswork out of Human Gene Editing
Technology
There are many good reasons to  criticize  Chinese researcher He Jiankui for reportedly gene-editing two human babies  — not only did his actions violate several accords within the scientific community, but he also undertook the project without proper transparency and oversight, working mostly in secret.

Worst of all, though, is the fact that He’s edits could affect the twin babies in unexpected ways. We don’t yet know how to ensure that CRISPR edits in humans do exactly what we want them to do — but that could be starting to change.

“The effects of CRISPR were thought to be unpredictable and seemingly random,” Francis Crick Institute researcher Paola Scaffidi said in a news release , “but by analysing hundreds of edits we were shocked to find that there are actually simple, predictable patterns behind it all.”

In a paper published in the journal Molecular Cell on Thursday, Scaffidi and his Crick colleagues describe a set of simple rules they believe take some of the guesswork out of human gene editing.

The first of those rules involves the region a researcher instructs CRISPR to target. If a certain genetic letter (G) is in a certain place (fourth letter from the end of the target sequence), the edit will likely result in many imprecise deletions. The solution: avoid targeting those regions.

The second involves the target DNA’s degree of “openness” during the CRISPR edit. The team discovered that the use of compounds that forced DNA to open up resulted in more efficient editing.

“We hadn’t previously appreciated the significance of DNA openness in determining the efficiency of CRISPR genome editing,” researcher Josep Monserrat said. “This could be another factor to consider when aiming to edit a gene in a specific way.”

While these rules may have arrived too late to protect the twin babies on the receiving end of He’s CRISPR edits, they could put us on the path to a future in which we can edit the genes of humans without worrying about unintended consequences.

“Until now, editing genes with CRISPR has involved a lot of guesswork, frustration, and trial and error,” Scaffidi said, later adding, “This will fundamentally change the way we use CRISPR, allowing us to study gene function with greater precision and significantly accelerating our science.”

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