October 22, 2020

The Niche

Knoepfler lab stem cell blog

Mitalipov briefly responds to Egli preprint, stands by human embryo CRISPR pub findings

Shoukhrat Mitalipov
Shoukhrat Mitalipov points to an image of a CRISPR edited human embryo inside an incubator at the Center for Embryonic Cell and Gene Therapy in Portland, Ore.
Rob Stein/NPR.org

There has been a wave of intense discussions both in the public domain such as on Twitter and behind the scenes over the new Egli, et al. preprint that challenges the main conclusions of the Ma, et al. Nature paper from Shoukhrat Mitalipov’s lab.

Ma, et al. reported CRISPR gene editing of human embryos, arguing for a mechanism of HDR-based gene editing relying on interaction of the maternal and paternal genomes in the early embryos. Egli, et al. presented several alternative explanations — mostly involving what would be artifactual outcomes — for why the Mitalipov team saw what they did in the human embryos.

I’m not an embryologist or recombination guru myself, but I’ve been brushing up on them this week, and still don’t quite get how the HDR between the genomes could have happened. But there is a lot of uncertainty about this situation. For all we know, Mitalipov’s team could generally be right, but we all just need more information to understand why as well as what potentially unusual biology and genetics explains it.

Below is a statement from Mitalipov in response to this situation, where he stands by their main conclusions:

“The study co-authors and OHSU welcome scientific discussion and inquiries of our peer-reviewed study published on Aug. 2 in the journal Nature. Our research uncovered a novel mechanism of DNA repair in human embryos, as well as a method to eliminate mosaicism.

“We recognize that these results must be confirmed by additional studies, and that independent verification of important new findings is a cornerstone of science. We encourage other scientists to reproduce our findings by conducting their own experiments on human embryos and publishing their results.

“We stand by our study’s key finding that human embryos are capable of effectively repairing disease-causing mutations by using a normal copy of the gene from a second parent as a template. We based our finding and conclusions on careful experimental design involving hundreds of human embryos.

“The critique leveled by Egli, et al, offers no new results but instead relies on alternative explanations of our results based on pure speculation. We will respond to their critiques point by point in the form of a formal peer-reviewed response in a matter of weeks.”

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