病原性ミトコンドリアDNA変異を有するヒト卵細胞におけるミトコンドリア置換

¹Center for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
²Division of Reproductive &Developmental Sciences, Oregon National Primate Research Center, Oregon Health &Science University, 505 NW 185th Avenue, Beaverton, Oregon 97006, USA.
³Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
⁴Department of Cell Biology School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, New Jersey 08084, USA.
⁵Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
⁶Reproductive Medical Centre, Anhui Medical University, No 218, Jixi Rd, Shushan District, Heifei, Anhui 230022, China.
⁷IviGen Los Angeles, 406 Amapola Avenue, Suite 215, Torrance, California 90501, USA.
⁸Research Cytogenetics Laboratory, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
⁹Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.
¹⁰Knight Cardiovascular Institute, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
¹¹Department of Biomedical Engineering, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.

⁰Center for Embryonic Cell and Gene Therapy, Oregon Health &Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, USA.

まとめ

ミトコンドリア置換療法 (MRT) は,子どもに衰弱するミトコンドリアDNA (mtDNA) 変異を継承するのを防ぐことができます. 複製効率と特定のポリモルフィズムに影響されるドナーのmtDNAの互換性は,胚性幹細胞の安定維持に不可欠です.

スピンドル移植は母親のmtDNAを成功裏に置き換え,結果として発生した胚で> 99%のドナーmtDNAを達成しました.
ドナーのmtDNAはほとんどのES細胞系で安定的に維持されたが,一部では母性ハプロタイプへの漸進的な損失と逆転を示した.
mtDNAの互換性は,単純な不一致または酸化リン酸化機能ではなく,複製効率と特定のポリモルフィズム (例えば,Dループの保存された配列ボックスII) と関連しているようです.

まとめ