22 March 2019
ESHRE supports the call for a moratorium on the use of CRISPR/Cas9 nucleases in the human embryo for clinical applications (Nature 567, 165-168 (2019)). This powerful genetic tool can be programmed easily to facilitate the correction of genetic mutations seamlessly and at high efficiency. Although the technology is already revolutionizing preclinical biomedical research, multiple independent reports have raised awareness that the CRISPR/Cas9 system can cause unexpected alterations to genomic DNA resulting in potentially damaging mutagenic events.
Firstly, the nuclease can cause mutation to the genome at closely matched sequences to the target gene, so called off-target mutations. Secondly, recent reports have shown that the enzyme can also cause unexpected large deletions and rearrangements at the actual target site, which could have considerably larger mutagenic effects . Lastly, when applied within the fertilized zygote, the persistence of the enzymes after the first cell-cleavage event can lead to a mosaic outcome, where different cells within a single embryo would harbour different mutations. The downstream consequences of non-specific mutagenesis off-target, genomic rearrangement on-target, and unpredictable mosaicism, are clearly hard to predict but have considerable potential to limit the safety of the CRISPR/Cas9 system for therapeutic intervention.
The ethics of germline genome editing are being widely discussed and debated, but all stakeholders agree that this technology can only be considered for clinical application if it is deemed safe. Research scientists are busy trying to understand the frequency and prevalence of these unexpected events and are developing new technologies to help eliminate them. Until such a time when the risks can be quantified or next generation tools developed which eliminate these disadvantageous consequences, ESHRE strongly supports the view that clinical application of CRISPR/Cas9 gene editing within the human zygote should not be performed.
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