相关实验视频
Updated: May 7, 2025
08:31
Porous Silicon Microparticles for Delivery of siRNA Therapeutics
Published on: January 15, 2015
10.9K
可电离聚合物微粒 (IPM) 提供有效的siRNA传递.
Ziyu Zhou1,2, Yu Feng1, Mingzhou Jiang3
1Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, PR China.
Nature communications
|January 3, 2025
概括
新的可电离聚合物微粒 (IPM) 提供了改进的siRNA传递,克服了脂质纳米粒子的挑战. 这些新型细胞增强细胞吸收,降低免疫反应,并显示出治疗肝纤维化的前景.
科学领域:
- 生物技术和生物医学工程 生物技术和生物医学工程
- 纳米医学是一种纳米医学.
- 药物输送系统 药物输送系统
背景情况:
- 脂质纳米颗粒 (LNP) 对于核酸输送是常见的,但由于目标不佳和加速血液清理 (ABC) 效应而受到影响.
- 开发先进的输送系统对于克服LNP的局限性和提高治疗疗效至关重要.
研究的目的:
- 设计和评估新的可电离聚合微粒 (IPM) 作为替代siRNA传递系统.
- 评估IPM与LNP相比的向能力,细胞吸收,基因沉默功效和体内性能.
主要方法:
- 合成了三种可电离的寡合物 (IOs),与聚乙烯-聚乙烯甘醇 (PLA-PEG) 结合,形成IPMs.
- 在IPM中封装siRNA,并评估了溶酶体逃逸和基因沉默.
- 开发了纤维细胞激活蛋白抑制剂修饰的IPM (FAPi-IPMs),用于向向激活的肝星细胞 (HSC) 进行向输送.
- 在纤维化模型中评估了FAPi-IPM向特异性,原减少和肝炎缓解.
- 将IPM和FAPi-IPM与LNP进行比较,以了解ABC效应,PEG抗体的产生和活体中阿波利波蛋白吸附.
主要成果:
- 装有siRNA的IPM成功逃离了溶酶体,并使目标基因沉默.
- FAPi-IPMs证明了对肝细胞的HSC的增强向,导致减少原分泌和肝炎,有效治疗纤维化.
- 与LNP相比,IPM和FAPi-IPM表现出较低的ABC效应和较低的PEG抗体生成.
- 在IPM体内观察到最小的阿波利波蛋白吸附,使其与LNP区分开来.
结论:
- 可电离聚合物微粒 (IPM) 是一个有前途的核酸输送平台,具有独特的准能力.
- 与传统的LNP相比,IPM有效地减轻了加速血液清理效应,并降低了免疫性.
- FAPi-IPM系统通过选择性地静止肝纤维细胞中的关键纤维基因,显示出针对性治疗肝纤维化的潜力.
相关概念视频
02:30siRNA - Small Interfering RNAs
16.3K
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...
16.3K
02:30Small interfering RNAs (siRNA)
3.3K
3.3K
02:15Experimental RNAi
6.0K
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...
6.0K
01:23RNA Interference
25.7K
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...
25.7K