2015年4月
Selective elimination of mitochondrial mutations in the germline by genome editing
Cell
- 巻
- 161
- 号
- 3
- 開始ページ
- 459
- 終了ページ
- 469
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.cell.2015.03.051
- 出版者・発行元
- CELL PRESS
Mitochondrial diseases include a group of maternally inherited genetic disorders caused by mutations in mtDNA. In most of these patients, mutated mtDNA coexists with wild-type mtDNA, a situation known as mtDNA heteroplasmy. Here, we report on a strategy toward preventing germline transmission of mitochondrial diseases by inducing mtDNA heteroplasmy shift through the selective elimination of mutated mtDNA. As a proof of concept, we took advantage of NZB/BALB heteroplasmic mice, which contain two mtDNA haplotypes, BALB and NZB, and selectively prevented their germline transmission using either mitochondria-targeted restriction endonucleases or TALENs. In addition, we successfully reduced human mutated mtDNA levels responsible for Leber's hereditary optic neuropathy (LHOND), and neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP), in mammalian oocytes using mitochondria-targeted TALEN (mito-TALENs). Our approaches represent a potential therapeutic avenue for preventing the transgenerational transmission of human mitochondrial diseases caused by mutations in mtDNA. PaperClip
- リンク情報
-
- DOI
- https://doi.org/10.1016/j.cell.2015.03.051
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/25910206
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505837
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000353553600008&DestApp=WOS_CPL
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84928395483&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84928395483&origin=inward
- ID情報
-
- DOI : 10.1016/j.cell.2015.03.051
- ISSN : 0092-8674
- eISSN : 1097-4172
- PubMed ID : 25910206
- PubMed Central 記事ID : PMC4505837
- SCOPUS ID : 84928395483
- Web of Science ID : WOS:000353553600008