阴离子siRNAs在动物细胞中提供无载体基因沉默
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
概括
齐普核酸 (ZNA) 提供了一种无载体的方法,可以将siRNA输送到细胞中,绕过纳米粒子屏障. 这些合物在微小分子度下实现了选择性基因沉默.
科学领域:
- 分子生物学分子生物学
- 基因沉默是一种基因沉默.
- 核酸化学的核酸化学
背景情况:
- 通过siRNA介导的基因沉默需要有效的细胞内传递.
- 传统的基于纳米粒子的交付面临细胞外障碍.
- 无载体的方法可以克服这些局限性.
研究的目的:
- 为siRNA开发和评估一种新的无载体分子传递系统.
- 为了研究细胞吸收和基因沉默能力的阴阳性寡精-寡核酸合物 (ZNAs).
主要方法:
- 使用酸化物化学合成酸的寡精-寡核酸合物 (ZNA).
- 基于N/P充电比的细胞进入和细胞质访问的评估.
- 使用 luciferase 记者测试对选择性基因沉默疗效的评估.
主要成果:
- 当N/P电荷比超过1.5.5时,ZNAs证明了细胞进入和细胞质访问.
- 满足这种电荷比的阴阳性siRNAs实现了 luciferase 基因表达的选择性抑制.
- 在亚微粒度度范围内观察到有效的基因沉默.
结论:
- ZNAs代表了一个可行的无载体策略,用于细胞内siRNA传递.
- 这种方法绕过了与纳米粒子传递相关的细胞外壁垒.
- ZNAs可以实现强大而选择性的siRNA介导的基因沉默.
相关概念视频
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...
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...
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...
Small interfering RNAs (siRNA)
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...
piRNA - Piwi-interacting RNAs
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...


