液晶倒置脂质相封装siRNA增强脂质纳米粒子介导的转染
Roy Pattipeiluhu1,2,3, Ye Zeng1, Marco M R M Hendrix4
1Supramolecular and Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Nature communications
|February 12, 2024
概括
研究人员设计了具有特定内部结构的脂质纳米粒子 (LNP),以改善RNA输送. 在LNP中预编程的六角相提高了用于治疗的小干扰RNA (siRNA) 传递效率.
科学领域:
- 纳米技术纳米技术
- 生物化学 生物化学
- 材料科学 材料科学 材料科学
背景情况:
- 有效的RNA分子细胞质传递对于RNA疗法至关重要,但仍然是一个重大挑战.
- 脂质纳米颗粒 (LNP) 是细胞内RNA传递的先进载体,特别用于SARS-CoV-2疫苗.
研究的目的:
- 合理设计和组装具有可编程脂质相的LNP,以增强小干扰RNA (siRNA) 封装和传递.
- 研究这些LNP的结构特征及其对细胞内静音效率的影响.
主要方法:
- 采用了自下而上的合理设计方法来创建具有特定脂质相的LNP.
- 利用冷传输电子显微镜,冷电子断层扫描和小角度X射线散射来分析LNP结构.
- 将LNP的细胞内静音效率与反向六边形相相对应的状相进行比较.
主要成果:
- 成功形成的LNP含有反向六角形液晶相.
- 证明,与状LNP相比,具有反向六角相的LNP表现出更高的细胞内静音效率.
- 观察到,具有预编程六角相的LNP通过绕过现场相位过渡来促进更有效的单步交付机制.
结论:
- 具有定义的内部脂质结构的LNP的合理设计,特别是反向六角相,显著提高了siRNA传递效率.
- 了解纳米-生物接口和LNP结构过渡是优化LNP设计和治疗应用的关键.
- 这项工作为开发和应用先进的基于LNP的RNA传递系统提供了宝贵的见解.
相关概念视频
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...
02:30siRNA - 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...