(From left) Professor Hyunji Lee (Korea University School of Medicine), Professor Seonghyun Lee (Department of Medicine and MetabioHealth, Sungkyunkwan University), Professor Jinsoo Kim (National University of Singapore, CTO of Edgen Co., Ltd.) , Researcher Seongho Hong (Korea University Medical School) and Dr. Seongik Cho (Yonsei University Medical School), Dr. Gayoung Lim (Korean Institute of Science and Technology KIST Brain Science Research Institute)
[메디칼업저버 신형주 기자] The possibilities for treating maternally inherited mitochondrial diseases are expected to increase.
The research group of Professor Hyunji Lee (co-first author, researcher Seongho Hong) of the Department of Convergence Medicine, Korea University College of Medicine, and the research group of Edgegene (CTO Jinsoo Kim) are the first in the world to transform the base of adenine (A) to guanine (G) in a specific sequence of mitochondrial DNA. Successfully created a mouse.
Mitochondria, the energy source within cells, contain mitochondrial DNA, which contains the genetic information for proteins that play an essential role in energy metabolism.
This DNA defect leads to mitochondrial failure and manifests itself in various diseases of the brain, nerves and muscles.
Furthermore, due to the nature of mitochondria, which are passed down only through maternal inheritance, the mother’s mitochondrial defect can be passed on to her children, resulting in mitochondrial disease.
Currently, CRISPR-Cas9 technology is used as a DNA editing technology, but it has a limitation in that it cannot be used for mitochondrial DNA editing because the guide RNA used to recognize specific DNA sequences cannot be transported throughout inside the mitochondria.
As a result, the mitochondrial DNA editing technology developed to date includes four types of DNA base sequences: adenine (A), guanine (G), thymine (T), and cytosine (C). Among the bases, cytosine (C) can be corrected to thymine (T). There is a proofreading enzyme (hereinafter referred to as DdCBE) and a base-correcting technology (transcription activator-like effector-linked deaminase (hereinafter referred to as TALED)) that can correct the base of adenine (A) into guanine (G).
Among them, there are research cases where mice were produced with mitochondrial C to T gene correction using DdCBE, but no cases of successful mitochondrial A to G gene correction have been reported in animal experiments using TALED .
The researchers confirmed that the previously developed TALED caused inadvertent random changes to DNA and RNA within cells.
It turned out that when TALED was injected into a fertilized mouse egg, embryonic development did not occur normally.
Accordingly, we have developed an improved TALED (V28R-TALED) so that the protein that mediates DNA modification among the constituent proteins of TALED can exhibit more precise activity and, through this, random modifications of DNA and ‘RNA in cells, which are side effects of TALED, are significantly reduced.Confirmed.
By microinjecting the improved TALED into a fertilized mouse egg, the company was able to produce a disease model that harbors a mutation in the mitochondrial disease “Leigh syndrome” and demonstrates the condition.
Co-first author Dr. Cho Seong-ik said, “Mitochondrial genetic diseases often cause severe symptoms, and I think this study is a good example of Korean researchers developing new technologies to overcome them and advance the technology.” stating, “We will continue to focus on technological development and side effect research to offer hope and possibilities for overcoming mitochondrial genetic diseases.”
Researcher Seongho Hong, co-first author, said: “It’s a great honor just to be able to participate in gene editing research to solve mitochondrial disease and help make it happen.” where research findings can give hope to others. “I am even happier to have achieved such a great result,” he said.
Professor Hyunji Lee, who led the research, said: “This study, which identified inadvertent random DNA and RNA modifications in existing mitochondrial gene editing technology, improved it and successfully applied it to animals, is a research that must be conducted before mitochondrial technology is changed.” gene editing technology can be developed as a treatment.” he said: “I am happy that we are one step closer to opening a path towards treatment for mitochondrial disease, for which until now there has been no adequate treatment .”
Meanwhile, this study was conducted by Cell, a world-renowned international academic journal.
#Development #animal #model #maternally #inherited #mitochondrial #disease
