Gene editing may result in human embryonic chromosomal serious confusion

Posted by on July 21, 2020 12:06 am
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gene editing may result in human embryonic chromosomal serious mess

recently, scientists carried out a series of use of CRISPR-Cas9 editing of human embryonic genomic experiments. The results revealed that the process is likely to target site or its vicinity in the genome resulting in unnecessary huge change.

these three independent studies have been published on the Preprint server bioRxiv, and reveals the CRISPR–Cas9 gene editing of new risks. Previous studies showed that CRISPR–Cas9 induced off-target mutations often occur in the distance of the target point is the far position. But recent studies have 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.

Anugeneticscientists Gaétan Burgio said the targeting effect is more important, more difficult to eliminate.

edit human embryos to prevent genetic diseases, the safety debate continues, because to do so would on the genome to cause permanent, can beGeneticchange.“ 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.” University of California, Berkeley study of gene editing Fyodor Urnov said.

in 2015, researchers in the laboratory for the first time to use CRISPR to edit the human embryo. Since then, the worldwide research team began to try this process, the purpose is the gene for precise editing. But such studies are still few, and usually subject to strict supervision.

CRISPR-Cas9 gene editing is the key to the cells in the active fix is to cut the DNA.“ These latest research tells us, people on this process of understanding is not enough.” Newcastle University reproductive biologist Mary Herbert said, with a Cas9 enzyme to attack DNA before, we need to fully understand the cells exactly what will happen.

the British Francis Crick Institute for Developmental Biology home Kathy Niakan team in a 6 on 5, in bioRxiv published 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 is happening around a large number of mutations, including DNA rearrangements and thousands of bases missing. This far exceeded the researchers ‘ expectations.

another study by the United States Columbia University,stem cellsbiologists Dieter Egli laboratory, they tried to use CRISPR-Cas9 to correct EYS2 gene mutation, this mutation will lead to blindness. Gene editing, about half the embryo missing a large number of chromosome fragments, and sometimes even the EYS gene where the entire chromosomes.

a third study is a United States Oregon Health and Science University reproductive biologist Shoukhrat Mitalipov research group in charge. They studied with trigger heart disease mutant embryos, also found that the CRISPR-Cas9 editing will affect the target site where the chromosome.

these unintended consequences is a DNA repair mechanism brings. CRISPR-Cas9 through a small segment of RNA, the Cas9 enzyme is positioned to the target site, and then Cas9 to cut two DNA strands, and finally the cell will fix this double-stranded gap.

gene editing is in the repair process to happen. Normally, 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 disorder or chromosomeMissing.

previous studies have shown that in mouse embryos or human cells using the CRISPR editing will result in unnecessary huge impact. However, Urnov said that 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.

previous studies usually focus on only a single or a 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, Urnov believes that the scientific community should be more carefully treat this issue, not the heart save a Fluke.

three studies proposed different mechanisms to explain the observed phenomenon. Egli and Niakan team the embryos were observed in most of the changes attributed to the large number of deletions and rearrangements. Mitalipov team believes they found the mutation in 40% by gene conversion cause. (Bio ValleyBioon.com）

Published at Tue, 21 Jul 2020 04:06:01 +0000

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