カチオンのsiRNAは,動物細胞のキャリアフリー遺伝子サイレンスを提供します
Marc Nothisen1, Mitsuharu Kotera, Emilie Voirin
1Laboratoire de Chimie Genetique, Universite de Strasbourg and C.N.R.S., Faculte de Pharmacie, 67401 Illkirch, France.
Journal of the American Chemical Society
|November 26, 2009
まとめ
Zip核酸 (ZNAs) は,ナノ粒子バリアを回避して,siRNAを細胞に届けるためのキャリアレス方法を提供します. これらのコンジュガートは,サブミクロモラー濃度で選択的な遺伝子サイレンシングを達成します.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子サイレンシング
- 核酸化学 核酸化学について
背景:
- siRNA媒介による遺伝子静止は,効果的な細胞内伝達を必要とします.
- 従来のナノ粒子ベースの配送は,細胞外の障壁に直面しています.
- キャリアレスアプローチは,これらの制約を克服することができます.
研究 の 目的:
- siRNA.のための新しいキャリアレス分子伝達システムを開発し,評価する.
- カチオン性オリゴスペルミン-オリゴヌクレオチド結合体 (ZNAs) の細胞吸収と遺伝子静止機能を調査する.
主な方法:
- フォスフォラミジット化学を用いたカチオン性オリゴスペルミン-オリゴヌクレオチド結合体 (ZNA) の合成.
- N/P充電比に基づくセルラーエントリーとサイトプラズマアクセスの評価.
- ルシフェラーゼレポーターアッセイを用いた選択的遺伝子静止効果の評価.
主要な成果:
- ZNA は,N/P 充電比が 1.5.5 を超えたとき,細胞への侵入と細胞質へのアクセスを実証しました.
- この電荷比を満たすcationic siRNAsは,ルシフェラーゼ遺伝子発現の選択的阻害を達成しました.
- 効果的な遺伝子サイレンシングは,サブマイクロモラー濃度範囲で観察されました.
結論:
- ZNAは,細胞内シRNA伝達のための実行可能なキャリアレス戦略を表しています.
- このアプローチは,ナノ粒子配送に関連する細胞外バリアを回避します.
- ZNAは,強力で選択的なsiRNA媒介遺伝子サイレンシングを可能にします.
関連する概念動画
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In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
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