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Chinese scientists test CRISPR on monkeys and find no off-target mutations

Date: 22.6.2018 

With the first UK and US human trials using the potentially revolutionary CRISPR gene editing technique about to commence, several questions still hover over the ultimate safety of this system. A team of Chinese scientists has now conducted the first full assessment of the effects of CRISPR-Cas9 on non-human primates to ascertain whether it results in off-target mutations. 

A controversial study published last year suggested CRISPR could introduce unintended mutations, but after several scientists criticized the veracity of the data it was ultimately retracted.

Despite the earlier flawed research being retracted, there are still major concerns that gene-editing using the CRISPR technique can potentially result in unintended mutations. The Chinese research is the first to perform a genome-wide evaluation on the connection between the CRISPR process and de novo mutations – new mutations that spontaneously arise in a fertilized egg during the initial stages of embryogenesis – in rhesus macaque monkeys.

The study began by using the CRISPR system on macaque zygotes, or fertilized eggs. The researchers were testing the effectiveness of the technique's targeting specificity by focusing on the deletion of a gene called MCPH1, known to cause birth defects in humans. In the embryos initially treated, the process successfully knocked the MCPH1 gene out in 13 out of 15 samples.

Five monkeys were ultimately gestated, with four surviving delivery. All the offspring monkeys displayed successful CRISPR modifications. Several techniques revealed that there were in fact no detectable off-target effects, but some de novo mutations were ultimately identified. Close study of the particular mutations detected in the monkeys led the researchers to safely conclude that these de novo mutations were regular spontaneous mutations and not related to the CRISPR process.

 


 

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