开发长非对称的siRNA结构,用于哺乳动物细胞中杀基因和免疫刺激
Soonkap Kim1, Young Gyu Kang1,2, Jaejin Kim1
1Department of Chemistry, Sungkyunkwan University, Suwon, Korea.
Nucleic acid therapeutics
|October 5, 2023
概括
较长的不对称的小干扰RNAs (asiRNAs) 显示了基因沉默的减少,但互补的突起增强了疗效. 这些双功能的asiRNAs可以触发免疫反应,同时对治疗潜力进行基因沉默.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 在RNA治疗方面,RNA疗法.
背景情况:
- RNA干扰 (RNAi) 对于转录后基因调节至关重要.
- 与传统的siRNA相比,不对称siRNA (asiRNA) 提供了改进的基因沉默,具有较少的非目标效应.
研究的目的:
- 研究导链长度对asiRNA基因沉默效率的影响.
- 为了评估asiRNAs的免疫刺激能力.
- 探索用于治疗应用的双功能亚基RNAs的开发.
主要方法:
- 产生长长的asiRNAs (lasiRNAs),指导链长度从25到29个核酸.
- 对基因抑制活性和Ago2结合亲和力的分析.
- 将类似收费受体 (TLR) 免疫反应动机纳入asiRNA结构.
主要成果:
- 随着指导链长度的增加, lasiRNAs 的基因沉默活性下降.
- 与目标基因互补的3'-end突起显示出更高的沉默效率.
- 通过结合免疫动机来诱导TLR特异性免疫反应,同时保持基因沉默活性.
结论:
- 可以优化 asiRNA 结构,以增强基因沉默和减少目标外影响.
- 可以将asiRNAs设计为双功能分子,将基因沉默与免疫刺激相结合.
- 这些发现为开发具有治疗潜力的免疫刺激性asiRNA铺平了道路.
相关概念视频
siRNA - Small Interfering RNAs
16.8K
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...
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...
16.8K
Experimental RNAi
6.2K
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...
6.2K
RNA Interference
26.1K
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...
26.1K
MicroRNAs
3.0K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
piRNA - Piwi-interacting RNAs
6.9K
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...
6.9K
Small interfering RNAs (siRNA)
3.6K
3.6K


