遺伝子編集は,ドゥシェンヌ筋縮症の犬のモデルでディストロフィン発現を回復する
Leonela Amoasii1,2, John C W Hildyard3, Hui Li1
1Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Science (New York, N.Y.)
|September 1, 2018
まとめ
デュシェンヌ筋縮症 (DMD) の犬のモデルでは,遺伝子編集により,ダイストロフィンタンパク質が成功しました. このアプローチは 筋肉の整体性と機能を改善することで DMDの治療に 有望な結果を示しています
科学分野:
- バイオテクノロジー
- 遺伝学
- 分子生物学
背景:
- デュシェンヌ筋縮症 (DMD) は,ディストロフィン遺伝子の変異によって引き起こされます.
- ヒトのDMD変異のホットスポットを模倣しています
- 筋肉の整体性や機能には ダイストロフィンの回復が不可欠です
研究 の 目的:
- 大型の動物モデルにおけるディストロフィン発現の回復のためのCRISPR遺伝子編集を評価する.
- 骨格および心筋におけるアデノ関連ウイルス (AAV) 媒介遺伝子編集の有効性を評価する.
主な方法:
- 4匹のDMD犬にAAVを介してCRISPR遺伝子編集成分を投与した.
- 投与方法は筋肉内投与と全身投与でした.
- 産後6~8週間でディストロフィンタンパク質発現を分析した.
主要な成果:
- 骨格筋におけるディストロフィン濃度が正常値の 3- 90% に回復した.
- ある犬では心臓筋ジストロフィン濃度が正常値の92%に達した.
- 治療を受けた犬は筋肉組織が改善した.
結論:
- AAVによるCRISPR遺伝子編集は,DMDの大型動物モデルでディストロフィンを再生できます.
- これらの発見は,DMDの治療のための遺伝子編集の臨床的可能性を裏付けています.
- この治療戦略を最適化するためにさらなる開発が必要である.
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