분자유전학실험실 (단국대학교 분자생물학과)



 이성욱 ( 2016-02-02 11:13:07 , Hit : 877
 CRISPR Editing of Human Embryos Approved in the U.K.

GEN News Highlights

Feb 1, 2016

Preserving the distinction between research purposes and clinical applications, the Human Fertilisation and Embryology Authority (HFEA), a U.K. regulatory body, has approved the use of CRISPR gene editing on human embryos. The HFEA indicated that its approval was specific to an application tendered by researchers at the Francis Crick Institute, who could begin their work “within the next few months,” provided they also secure the approval of a local ethics body.

The Crick’s research, which will be led by Kathy Niakan, Ph.D., is aimed at understanding the genes human embryos need to develop successfully. Details of the proposed work appeared in September 2015, when the Crick researchers submitted their application to the HFEA.

"To provide further fundamental insights into early human development, we are proposing to test the function of genes using gene editing and transfection approaches that are currently permitted under the HFE Act 2008,” said Dr. Niakan at the time. “We also propose to use new methods based on CRIPSR/Cas9, which allows very specific alterations to be made to the genome. By applying more precise and efficient methods in our research we hope to require fewer embryos and be more successful than the other methods currently used.”

In response to the current announcement, Paul Nurse, Ph.D., director of the Crick, noted that Dr. Niakan's proposed research is “important for understanding how a healthy human embryo develops. It will enhance our understanding of IVF success rates,” he continued, “by looking at the very earliest stage of human development—one to seven days." During this stage of development, a single cell gives rise to around 250 cells. In the Crick’s investigations, development will be stopped at this point and the embryos destroyed.

In line with HFEA regulations, any donated embryos will be used for research purposes only and cannot be used in treatment. These embryos will be donated by patients who have given their informed consent to the donation of embryos that are surplus to their IVF treatment.

The current announcement follows HFEA deliberations that were detailed in the minutes of a meeting that took place on January 14. The minutes indicate the kinds of questions that were raised by proposed use of the CRISPR/Cas9 technique:

“One of the peer reviewers had suggested using alternative techniques for gene disruption, such as gene expression knock-down using RNA interference (shRNA), instead of CRISPR/Cas9,” the minutes read. “However the Committee was satisfied that CRISPR/Cas9 had, in other studies, produced results suggesting that it was a highly efficient and targeted method of gene disruption, potentially superior to other techniques that were available.”

The minutes also described the aims of the Crick’s research:

1. Determine the relationship between the cellular and molecular properties of human preimplantation embryos and human embryonic stem cell lines.

2.Establish defined, animal product–free conditions for the derivation of pluripotent human embryonic stem cell lines, ultimately leading to Good Manufacturing Practice–compatible approaches.

3.Establish and characterize human extraembryonic stem cell lines.It is with respect to the first aim that the CRISPR technique is most directly relevant. This technique, the researchers say, will allow functionally testing of the requirement of human-specific genes during embryonic development.

“Our recently published RNA sequencing data demonstrate several genes and signaling pathways that are specifically expressed during human embryo development, compared with mouse,” the researchers indicated. “Many of our candidate regulatory genes are also expressed in [human embryonic stem cell (hESC)] lines. Therefore, gene-editing approaches will be optimized in hESC lines, prior to experiments using embryos. However, while we showed that hESC have a related gene expression state to the epiblast in the embryo, they are far from identical, which means that ultimately, we need to test the function of genes directly in the human embryo to determine if they are necessary for development.”

Initially, the Crick’s research will focus on the Oct4 regulatory factor, deficiencies of which are associated with the inability to generate embryonic stem cells in mice. According to the Crick team, there is evidence of temporal distinctions in the expression dynamics of OCT4/Oct4 between humans and mice. “It is therefore important to functionally test the requirement of factors such as OCT4 in human embryogenesis, to directly test conserved versus specific roles compared to the mouse,” say the researchers. “As OCT4 is likely to play a role, this gene will also serve as a first proof of concept.”

Following OCT4, the researchers will focus on human-specific epiblast enriched genes, such as KLF17, which the Crick team we recently identified. The Crick team also looks forward to investigating several human-specific factor, whose expression is absent in any of the pluripotent stem cell lines established to date, such as ARGFX.








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