Genome Editing Human Embryos

It seems that the ethical buzz was coming from a paper by a unknown Chinese group not involved with any of the genome editing pioneers. They took the unviable leftovers from In Vitro Fertilization (IVF) and then genome edited these human ’embyros’.

Interestingly, the success was quite poor. There was:

  • A Low Editing Rate
  • Toxicity
  • Rampant Off-Target effects

This in stark contrast to the use of CRISPR/Cas9 in dozens of animals ranging the entire tree of life. Ultimately, it doesn’t appear to be human limitation, as mammals including monkeys have been done much more successfully, but rather a result of poor experimental design, as these effects can be almost entirely attenuated by good guide RNA design and it seems that they didn’t considers the different chromatin states of embroynic stem cells that would influence off-target effects.

This was probably due to rushing the design in order to claim to be the first to alter human embryos, as opposed to the much more informative, well done, and ethically appeasing altering of Human Embryonic Stem Cells (HESCs) that showed off human CRISPR/Cas9 genome editing can be done properly in germ-line cells, with all its perks, and lead to breakthrough at the basic level in addition to all the clinical potential of genome editing technologies.

This speculation is apparent as there was a large outcry when the Chinese authors tried the ‘high impact’ journals and it seems they settled on a much lesser known open access that has additional concerns with the peer review process, mainly that it took one day, instead of 6 months to a year of the purgatory that is usually is.

Ultimately, it seems this was rushed for fame of unknown researchers and unknown journal, rather than science. But it’s still a Pubmed indexed journal with an impact factor and published by Springer. It is a bit of a shame as the Pandora’s box of CRISPR in human embryos needed to be opened quite slowly and carefully. The parts are all relatively easily accessible and not restricted, which is what has lead to spectacular pace of CRISPR/Cas9 genome editing development. While the field has its leaders developing CRISPR for the clinic the proper way, the technology it is now at the place where it can be picked up by many more who may not just be interested in the somatic line. But here we are now, waiting to see if genome editing technology will change the world, by curing inherited human disease or being used to design sci-fi nightmares. Either way, human inheritance has entered the designer era.

Sources:

  1. The Primary Publication
  2. Nature News
  3. Stem Cell Assays

The Paper We’ve Been Waiting For? CRISPR/Cas9 in Human Embryonic Stem Cells

Well it seems it has been done, the paper showing off the stuff science fiction has come out. CRISPR/Cas9 was used in human embryonic stem cells by the Meissner group at Harvard featuring J. Keith Joung and John Rinn.

“Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells”

Nature Genetics

Abstract: “DNA methylation is a key epigenetic modification involved in regulating gene expression and maintaining genomic integrity. Here we inactivated all three catalytically active DNA methyltransferases (DNMTs) in human embryonic stem cells (ESCs) using CRISPR/Cas9 genome editing to further investigate the roles and genomic targets of these enzymes. Disruption of DNMT3Aor DNMT3B individually as well as of both enzymes in tandem results in viable, pluripotent cell lines with distinct effects on the DNA methylation landscape, as assessed by whole-genome bisulfite sequencing. Surprisingly, in contrast to findings in mouse, deletion of DNMT1 resulted in rapid cell death in human ESCs. To overcome this immediate lethality, we generated a doxycycline-responsive tTA-DNMT1* rescue line and readily obtained homozygous DNMT1-mutant lines. However, doxycycline-mediated repression of exogenous DNMT1* initiates rapid, global loss of DNA methylation, followed by extensive cell death. Our data provide a comprehensive characterization of DNMT-mutant ESCs, including single-base genome-wide maps of the targets of these enzymes.”