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Researchers warn of unintended effects from CRISPR genome editing

19 April 2021
Appeared in BioNews 1091

Using CRISPR/Cas9 genome editing in human embryos may introduce 'on-target' errors.

Researchers at the Francis Crick Institute, London, have looked into genome-edited human embryos from previous studies – including their own – and discovered that 16 percent of the embryos contained previously overlooked unintended gene changes.

'This work underscores the importance of testing for these unintended mutations to understand exactly what changes have happened in any human cell type,' said senior author Professor Kathy Niakan of the Francis Crick Institute and the University of Cambridge. 'It is important to understand these events, how they arise and their frequency, so we can appreciate the current limitations of the technology and inform strategies to improve it in the future to minimise these mutations.' 

CRISPR-based genome editing has gained popularity as a highly specific way to insert, remove and replace DNA sequences in a cell's genetic code. However, the use of this approach in humans is controversial due to the possibility of introducing unwanted mutations with potential side effects.

Previous studies have looked at off-target effects (unintended changes in parts of the genome away from the intended editing site), but the team from the Crick wanted to examine unintended changes introduced at or near the location of the planned editing - known as 'on-target effects'. 

In this study, published in PNAS, researchers looked at previous studies using genome editing in human embryos that had been donated by IVF patients who no longer needed them. These studies used CRISPR/Cas9 to create mutations in the POU5F1 gene in order to investigate its role in embryonic development. 

The team developed a novel, open-source computational pipeline that identifies unintended on-target mutations caused by CRISPR/Cas9. Examining 65 samples (25 CRISPR/Cas9 targeted, 16 Cas9 controls, and 24 unedited controls), researchers observed that 16 percent of the samples contained large unintended mutations next to or within the edited location in the genome.

'Conventional tests used to check the accuracy of CRISPR/Cas9 can miss the types of unintended on-target mutations we identified in this study,' said lead author Dr Gregorio Alanis Lobato. 'There's still so much for us to learn about the effects of CRISPR/Cas9'.

SOURCES & REFERENCES
CRISPR has a problem: It mangles DNA it wasn't supposed to touch
Neoscope |  12 April 2021
Frequent loss-of-heterozygosity in CRISPR/Cas9-edited early human embryos
Proceedings of the National Academy of Sciences of the United States of America |  9 April 2021
Researchers call for greater awareness of unintended consequences of CRISPR gene editing
The Francis Crick Institute |  9 April 2021
The genetic mistakes that could shape our species
BBC Future |  12 April 2021
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