Molecular Genetics and Genomics

, Volume 292, Issue 3, pp 535–536 | Cite as

Editor’s comment on “CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein”

Editor’s Commentary

The ethical aspects of genetic engineering have been discussed since the early 1970s, already then with the expectation that eventually it may be possible to perform targeted genetic changes in the human germline. Technically, however, this has not been feasible until very recently. The development of CRISPR/CAS9 technology has made it possible to perform with reasonable effort and specificity genetic changes in mammalian cells, including zygotes or embryos (Ledford 2015).

In this issue of Molecular Genetics and Genomics, we publish work by Tang et al. that, to our knowledge, for the first time, demonstrates in diploid (2N) human embryos the correction of genetic defects. The defects studied in this case are a mutation in the HBB (haemoglobin subunit beta) gene and one in the gene encoding the enzyme glucose-6-phosphate dehydrogenase (G6PDH). These rather common genetic defects cause different types of anaemia, β-thalassemia and favism, respectively. Previous work has already shown that CRISPR/CAS9 technology can be employed to perform specific changes in triploid (and hence non-viable) human embryos (Kang et al. 2016; Liang et al. 2015). Hence, the findings reported by Tang et al. are not surprising. However, in vitro inseminated and genetically altered 2N human embryos can principally be implanted and develop into human beings, thereby bringing genetic manipulation of the human germline one step closer to reality. The work reported in this issue of MGG demonstrates that, as expected, it is possible to perform gene editing in human zygotes/embryos for establishing, for instance, correction of genetic defects carried by the parents. The embryos generated in the present study were destroyed as part of the analysis.

The work by Tang et al. also points to limitations and complications. First of all, only a rather small number of embryos were investigated. Ten wild-type oocytes were inseminated with sperm from heterozygous patients. In the case of HBB (chromosome 11), this resulted in four heterozygous zygotes and in the case of G6PDH deficiency (X-chromosome) in only two female embryos heterozygous for the mutation. Of the four HBB zygotes, two were edited but just one by homology-directed recombination (HDR), which results in correct repair of the mutation. In the case of G6PDH deficiency both zygotes showed homology-directed editing and hence repair of the mutation. One of the two embryos was chosen for whole genome sequencing and no off-target genetic events were determined.

Far more work with a larger number of embryos will be required to demonstrate how the technology can safely be used for gene editing in human embryos. One critical aspect concerns the repair pathway employed by target cells following the CAS9-mediated double strand-break, i.e., HDR (which results in correct editing) or non-homologous end-joining (NHEJ), which results in other changes at the repair site. Such events were observed in the case of the HBB experiments. Another issue concerns the generation of mosaic embryos, which also were observed in this study. For instance, one of the two embryos in the G6PDH experiments contained wild type, corrected and edited cells at a ratio of 2:1:1.

It still appears a rather long way until gene editing in human embryos becomes feasible with high fidelity and safety. But the present and previous work implicate that those hurdles can probably be overcome, raising again a range of ethical aspects.

The editors of MGG considered carefully publishing the work of Tang et al. which was initially submitted already on July 8, 2016. The work was reviewed according to our standards by two independent experts, who saw three versions of the paper. Editors and publisher are in possession of the documentation concerning the ethical approval by local committees and the consent of donors. Our experts have carefully checked the manuscript and the documentation. We are aware of the fact that this research is not allowed in many countries. Still, we decided to publish the work because we believe that the scientific community should have access to the results obtained.

Previous publications of gene editing in human embryos (Kang et al. 2016; Liang et al. 2015) have received various commentaries (for instance: Callaway 2016; Ledford 2015, or http://www.kurzweilai.net/chinese-team-genetically-modifies-human-embryo-using-crispr-gene-editing-technique), which may serve as entry point for further reading on the discussion around the technology, its use and ethical considerations.

By publishing the work of Tang et al. in Molecular Genetics and Genomics the editors and the publisher do not take any position in the discussion about the application of gene editing in human embryos.

References

  1. Callaway E (2016) Second Chinese team reports gene editing in human embryos. Nature. doi:10.1038/nature.2016.19718 Google Scholar
  2. Kang X et al (2016) Introducing precise genetic modifications into human 3PN embryos by CRISPR/Cas-mediated genome editing. J Assist Reprod Genet 33:581–588. doi:10.1007/s10815-016-0710-8 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ledford H (2015) CRISPR, the disruptor. Nature. doi:10.1038/522020a Google Scholar
  4. Liang P et al (2015) CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 6:363–372. doi:10.1007/s13238-015-0153-5 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Biology and Biological EngineeringChalmers University of TechnologyGothenburgSweden

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