单链siRNAs在动物中激活RNAi
Walt F Lima1, Thazha P Prakash, Heather M Murray
1Core Antisense Research, Isis Pharmaceuticals Inc., Carlsbad, CA 92010, USA.
Cell
|September 4, 2012
概括
强大的单链siRNAs (ss-siRNAs) 可以在体内安静基因,而无需复杂的传递. 这一发现简化了RNA干扰 (RNAi) 疗法,并为RNAi机制提供了新的见解.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 小干扰RNAs (siRNAs) 的治疗应用受到复杂传递系统的需要所阻碍.
- 识别强大的单链RNA可以简化基于RNA的药物的开发.
研究的目的:
- 开发和表征单链siRNAs (ss-siRNAs),能够在体内无需脂质配方进行基因沉默.
- 探索ss-siRNAs的结构-活性关系,以提高功效,稳定性和药理动力学特性.
主要方法:
- 代设计和单链RNA的化学修饰.
- 结构-活性关系研究将化学修饰与阿尔戈纳特2 (AGO2) 活性,细胞效能,核酶稳定性和药理动力学相关联.
- 在体内测试ss-siRNAs的基因沉默功效.
主要成果:
- 确定了有效的ss-siRNAs,可以在没有基于脂质的输送的情况下使动物的基因表达沉默.
- 证明乘客链对于通过RNA干扰 (RNAi) 途径进行强有力的基因沉默并非必不可少.
- 证实了ss-siRNA在体内活动需要5'酸盐,从而产生稳定的5'-(E) - 乙烯基酸盐 (5'-VP) 模拟物.
结论:
- 强大的ss-siRNAs代表了RNAi疗法的简化方法,绕过了复杂的传递要求.
- 这些发现为RNAi的机制提供了新的视角,突出了导向链和5'酸盐的重要作用.
- 这项工作扩大了开发基于RNAi的药理学药剂的选择.
相关概念视频
02:30siRNA - 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...
02:15Experimental 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...
01:23RNA 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...
01:23RNA 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...
02:57piRNA - 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...
02:39lncRNA - Long Non-coding RNAs
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...