Mobile Menu

Check your CRISPR-Cas9 edits Cautions Crick

CRISPR-Cas9 is currently one of the most significant gene-editing tools. Its discovery won the Nobel Prize for Chemistry last year. It has also been hailed as having great clinical potential for correcting disease-causing mutations in somatic cells – and perhaps in the germline as well.

But what are the effects of gene-editing in this way? How accurate is CRISPR-Cas9 at editing the genome? Researchers from the Crick Institute analysed their own work to find out.

CRISPR-Cas9 Edits

Editing embryos is legal up until the embryo is 14 days old and is not allowed to be implanted into a womb. The clinical applications of editing germline cells are immense, potentially eradicating autosomal dominant diseases by removing the disease-causing allele. However, due to the actions of He Jiankui in 2018, when he created the first gene-edited babies to worldwide condemnation, this is likely to be a long way off.

Unintended mutations reported from CRISPR-Cas9 edits is nothing new, but the range and type of effects are still poorly characterised. One of the findings from this study was an increased loss of heterozygosity (LOH) in the embryos, along with a range of on-target mutations.

Loss of Heterozygosity

LOH refers to the loss of one parent’s genetic information at a particular point. So, previously heterozygous alleles become homozygous – something that is frequently noted in cancer cells. The discovery of increased LOH in human embryos after CRISPR-Cas9 gene editing is an understandable point of concern.

The Findings

Data was retrospectively analysed from previous research for changes to the genome. Specifically, in work focussed on OCT4, a protein active in the human embryo within the first few days of development. The embryos were at the blastocyst stage and donated by those undergoing IVF.

To do this, they developed an open-source computational pipeline to analyse several types of genomic data. This method was created as conventional tests can miss on-target mutations caused by CRISPR-Cas9.

Most were found to be small indels – which can have detrimental effects – but 16% were larger deletions or genomic rearrangements. Further investigation is being done to determine the exact nature of these effects.

Key Takeaways

The researchers call for all those using CRISPR-Cas9 to edit human cells to test for these unintended effects – especially those hoping to apply their work clinically. Until researchers can pinpoint when and how frequently these mutations occur the technology cannot be refined or applied.

Baby vector created by vectorjuice –

More on these topics

CRISPR / Embryo / Gene Editing