Why does CRISPR sometimes work sometimes not

[Alfred001]

I'm reading this article on CRISPR used in human embryos,

https://www.wired.com/story/crispr-base-editing-first-china/?mbid=social_twitter

and it says

Quote

Sequencing revealed that all 18 embryos had been edited, with 16 of the embryos bearing the corrected version of the FBN1 gene. In two of the embryos, additional unwanted edits had also taken place. Previously, the most successful demonstration of gene editing in the human germline was the correction of a mutation that causes a hereditary heart condition in 42 out of 58 embryos. That study, which was published last year, used standard Crispr cut-and-paste technology.

and I'm wondering, if the exact same thing was done in all the embryos, why do you get different results in some?

[Endy0816]

It can make mistakes in targeting.

Quote

Scientists initially thought that Crispr-Cas9 only cleaves a piece of DNA if it exactly matches the cheat sheet of RNA that it carries. However, that assumption has now been proven wrong. The protein sometimes cuts DNA sequences that resemble the material it is looking for, but that contain a number of different letters. According to researcher Martin Depken of Delft University of Technology, cutting such slightly differing sequences is very logical from an evolutionary point of view. "Viruses mutate constantly, and can therefore have a different genetic make-up than what Cas9 is looking for," he says. "By also cutting DNA sequences that are slightly different, the Crispr-Cas9 system can track the evolution of a virus and better protect the bacterium against its foes."

https://phys.org/news/2018-02-mathematics-crispr-cas9-wrong-dna.html

Still probably less random than other methods.

[Alfred001]

Thanks!