用多价性siRNA-纳米粒子合物进行基因调节
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
概括
我们开发了用于RNA干扰 (RNAi) 的新型RNA-金纳米粒子结合物. 这些纳米颗粒增强RNA稳定性和细胞吸收,导致有效的基因敲击,没有转染剂.
科学领域:
- 纳米技术纳米技术
- 分子生物学分子生物学
- 生物结合的生物结合
背景情况:
- RNA干扰 (RNAi) 是一种强大的基因沉默机制.
- 提供小干扰RNA (siRNA) 仍然是治疗应用的挑战.
- 黄金纳米颗粒为药物输送和生物结合提供了一个多功能平台.
研究的目的:
- 为了合成和表征多价RNA-金纳米粒子结合物 (RNA-Au NPs).
- 设计RNA-AuNP以提高RNAi通路中的稳定性和有效的细胞吸收.
- 在细胞模型中评估RNA-AuNP的基因淘汰能力.
主要方法:
- 合成金纳米颗粒的合成功能化与合成RNA寡核酸.
- 对于表面负荷和稳定性的RNA-AuNP的表征.
- 在体外细胞吸收和基因沉默功效的评估.
主要成果:
- 合成的RNA-AuNP表现出siRNA复杂体的高表面负荷.
- 与自由dRNA相比,结合物半衰期长6倍.
- RNA-Au NPs在没有转染剂的情况下促进细胞进入,实现了显著的基因淘汰.
结论:
- 多价RNA-AuNP是RNAi治疗的有前途的交付平台.
- 开发的纳米粒子克服了自由siRNA传递的关键限制.
- RNA-Au NPs显示了有效的基因沉默应用的潜力.
相关概念视频
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,...


