Researchers call for greater awareness of unintended consequences of CRISPR gene editing

CRISPR-Cas9 genome editing can lead to unintended mutations at the targeted section of DNA in early human embryos, researchers have revealed. This highlights the need for further research into the effects of CRISPR-Cas9 genome editing, especially when used to edit human DNA in laboratory research.

  DNA  Credit: Arek Socha on Pixabay

CRISPR-Cas9 genome editing is a widely used research tool which allows scientists to remove and replace sections of DNA in cells, allowing them, for example, to study the function of a given gene or to repair mutations. Last year the researchers who developed CRISPR-Cas9 were awarded the Nobel Prize in Chemistry.

In the study published in the journal PNAS, scientists retrospectively analysed data from previous research in which they had studied the role of the OCT4 protein in human embryos during the first few days of development.

The team found that while the majority of CRISPR-Cas9-induced mutations were small insertions or deletions, in approximately 16% of samples there were large unintended mutations that would have been missed by conventional methods to assess DNA changes. 

Research is ongoing to understand the exact nature of the changes at the target sites, but this could include deletions of sections of DNA or more complex genomic rearrangements. 

The discovery highlights the need for researchers who use CRISPR-Cas9-mediated genome editing to edit human cells, whether somatic or germline, to be aware of and test for these potential unintended consequences. This is even more essential if they hope their work will be used clinically, as unintended genetic changes like this could lead to diseases like cancer.  

“Other research teams have reported these types of unintended mutations in human stem cells, cancer cells and other cellular contexts, and now we’ve detected them in human embryos,” said Professor Kathy Niakan, group leader of the Human Embryo and Stem Cell Laboratory at the Francis Crick Institute and Professor of Reproductive Physiology at the University of Cambridge, and senior author of the study.

“This work underscores the importance of testing for these unintended mutations to understand exactly what changes have happened in any human cell type.”

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Image:   DNA

Credit: Arek Socha on Pixabay

Reproduced courtesy of the University of Cambridge



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