具有减少反应的siRNA结合凝纳米粒子用于基因沉默
Stuart S Dunn1, Shaomin Tian, Steven Blake
1Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Journal of the American Chemical Society
|April 6, 2012
概括
水凝纳米颗粒有效地提供小干扰RNA (siRNA) 进行基因沉默,无毒性. 这些PRINT制造的纳米粒子提供触发的siRNA释放,增强RNA干扰 (RNAi) 的治疗潜力.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术 纳米技术
- 分子生物学分子生物学
背景情况:
- 有效地提供RNA干扰 (RNAi) 疗法仍然是一个挑战.
- 基于脂质和聚合物的系统对于小干扰RNA (siRNA) 传递是常见的.
- 材料的安全性和兼容性对于最大限度地提高治疗指数至关重要.
研究的目的:
- 探索水凝纳米粒子作为RNAi治疗的输送载体.
- 从纳米粒子中开发一种控制siRNA释放的系统.
- 为了优化基因沉默效率和输送系统的细胞相容性.
主要方法:
- 使用非湿模板中的粒子复制 (PRINT) 来创建水凝纳米粒子.
- 封装的siRNA通过静电关联和物理捕获.
- 准备了一种可聚合的siRNA亲药结合物,与二硫化物结合用于触发释放.
主要成果:
- 经过PEGylated水凝证明了剂量依赖的基因沉默,使用低siRNA剂量并且没有细胞毒性.
- 在减少环境中观察到siRNA的触发释放,货物的完整性在生理上保持.
- 通过选颗粒氨基含量来优化基因沉默和细胞相容性.
- 使用可释放siRNA水凝,证明了具有最小细胞死亡的针对性基因淘汰.
结论:
- 由PRINT制备的凝纳米粒子是RNAi治疗的有希望的载体.
- 开发的亲药物合物可以触发siRNA释放,改善治疗控制.
- 进一步优化纳米粒子特性可以导致有效的活体RNAi疗法.
相关概念视频
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...
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...
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...