多価 siRNA-ナノ粒子結合体による遺伝子調節
David A Giljohann1, Dwight S Seferos, Andrew E Prigodich
1Department of Chemistry and International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, USA.
Journal of the American Chemical Society
|January 28, 2009
まとめ
私たちはRNA干渉 (RNAi) のための新しいRNA-ゴールドナノ粒子の結合体を開発しました. これらのナノ粒子はRNAの安定性と細胞の吸収を高め,トランスフェクション剤なしで効果的な遺伝子ノックダウンにつながります.
科学分野:
- ナノテクノロジー ナノテクノロジー
- 分子生物学は分子生物学である.
- バイオコンジュゲーションによるバイオコンジュゲーション
背景:
- RNA干渉 (RNAi) は強力な遺伝子サイレンスメカニズムである.
- 小型の干渉RNA (siRNA) の配送は,治療用途の課題であり続けています.
- 金ナノ粒子は,薬物投与と生物結合のための汎用的なプラットフォームを提供します.
研究 の 目的:
- 多価なRNA-ゴールドナノ粒子結合体 (RNA-Au NP) を合成し,特徴づけること.
- RNA-Au NPを設計して,安定性を高め,RNAi経路で効率的な細胞吸収を図る.
- 細胞モデルにおけるRNA-AuNPの遺伝子ノックダウン能力を評価する.
主な方法:
- 合成RNAオリゴヌクレオチドで機能化された金のナノ粒子の合成.
- 表面負荷と安定性に関するRNA-AuNPの特性.
- 細胞吸収と遺伝子静止効果の評価 in vitro.
主要な成果:
- 合成されたRNA-AuNPは,siRNA複合体の高い表面負荷を示した.
- 結合剤は,自由dRNAと比較して半減期が6倍長く示されました.
- RNA-Au NPsは,変異剤なしで細胞への侵入を容易にし,重要な遺伝子ノックダウンを達成しました.
結論:
- 多価RNA-AuNPは,RNAi療法のための有望な配送プラットフォームです.
- 開発されたナノ粒子は,自由 siRNA 配送の主要な制限を克服します.
- RNA-Au NPsは,効果的な遺伝子サイレンシングの応用の可能性を示しています.
関連する概念動画
RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
siRNA - Small Interfering RNAs
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
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...
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...
Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
Translational Regulation
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...


