Caution! Gene editing leads to embryonic chromosomal serious confusion

careful! Gene editing leads to embryonic chromosomal serious mess

author | Leon

responsible for encoding | snow on

recently, three independent studies show that< span class="bjh-strong">in human embryos CRISPR gene editing will cause a large number of DNA deletion and reorganization。 These results will increase awareness of gene editing security concerns.

of human embryos for gene editing has always been a controversial thing figure source: Pascal Goetgheluck/Science Photo Library

recently, scientists conducted a series of use of CRISPR-Cas9 editing of human embryonic genomic experiments. The results revealed that in the target position near the point of introduction of a large number of unnecessary changes.

three separate studies were from the UK Francis Crick Institute Kathy Niakan Research Group, the United States Columbia University Dieter Egli laboratory and Oregon Health and Science University/Shandong University of Shoukhrat Mitalipov research group, have been uploaded to the Preprint serverbioRxivon【1-3】.

span class=”bjh-strong”>these studies reveal the CRISPR–Cas9 gene editing new venture。 Previous research has shown that CRISPR–Cas9 induced off-target mutations often occur in the distance of the target point is the far position. A recent study, researchers found that not only is the target site within the CRISPR–Cas9 in target position near the point of introduction of unwanted mutations, which is the traditional method can not be detected. Gene editing field scholars Gaétan Burgio believe that these“on-target”effect is more difficult to avoid.

whether it should be edited in human embryos to prevent genetic disease debate has been going on.< span class="bjh-strong">the reason this is controversial is because to do so would of the genome resulting in a permanent, heritable changeit.“ If put to reproductive purposes of human embryonic gene editing activity than is space flight, then the latest research is equivalent to the launch pad does not take off in the rocket to blow up.” At the University of California at Berkeley to study gene editing Fyodor Urnov said.

unexpected Editing consequences

in 2015, The Sun Yat-sen University the Yellow Army’s laboratory for the first time to use CRISPR to edit the human embryonic【4】。 Since then, all over the world the team began to try this process. But such studies are still few, and usually subject to strict supervision.

CRISPR-Cas9 gene editing, the key step is, cells actively repair is to cut the DNA. These latest research tells us, people on this process of understanding is still far from enough. Biologist Mary Herbert said, with a Cas9 enzyme to attack DNA before, we need to fully understand the cells exactly what will happen.

London, United Kingdom the Francis Crick InstituteKathy Niakanthe research group at the 6-month 5, inbioRxivpublished the first paper. In this study, the researchers used CRISPR-Cas9 in the POU5F1 gene in the introduced mutations, the gene for the embryonic development is very important. In 18 is the edit of the embryo, about 22% was detected in POU5F1 around a large number of mutations, including DNA rearrangements and thousands of bases missing. This far exceeded the researchers ‘ expectations.

another study by Columbia University’s Dieter Egli laboratory, they tried to use CRISPR-Cas9 to correct EYS gene mutations, this mutation can cause blindness. After editing, approximately half of the embryos missing a large number of chromosome fragments, and sometimes even the EYS gene where the entire chromosomes.

by the Oregon Health and Science University/Shandong University of Shoukhrat Mitalipov led a third group of researchers studied the with raised heart disease mutant embryos. Similarly, they found that the CRISPR-Cas9 editing will affect the target site where the chromosome.

it is difficult to predict the DNA repair

these unintended consequences is the DNA repair mechanism of the。 CRISPR-Cas9 technology through the guide RNA, the Cas9 enzyme is positioned to the target site, and then Cas9 put the two strands of DNA cut off, and finally the cells themselves will repair this double-stranded gap.

gene editing is in the repair process to happen. In General, cells use an error-prone mechanism to fix the gap, the result is a small amount of bases inserted or deleted. If artificially to the cells to provide template DNA, cells sometimes use this template to repair the gap, thereby introducing new DNA sequences. However, DNA double-strand breaks also lead to the DNA sequence of the confusion or chromosomes are missing.

previous studies have shown that, in mouse embryos or human cells using the CRISPR editing will result in huge, unnecessary influence of【5 and 6】。 However, in the human embryo in the completion of this work is also very important because different cell types may have on gene editing to make different reaction.

prior studies usually only focus on a single or few nucleotide mutations, thereby missing such large-scale chromosomal mutation.the latest of three studies looking specifically for these target sites in the vicinity of large-scale mutations, the scientific community should be more carefully treat this issue, not the heart save a Fluke.

the bewildering molecular mechanisms

three studies proposed different mechanisms to explain the observed phenomenon.Francis Crick Institute and Columbia University researchers in the embryo observed in most of the changes attributed to the large number of deletions and rearrangements. Oregon Health and Science University/Shandong University, the research team believes that they found the variation that 40% by gene conversion gene conversions caused it.

Published at Sun, 28 Jun 2020 21:10:05 +0000