修改后的双胞胎阴离子环氧的结构-活性关系,用于增强siRNA传递
Ayse Kont1, Monique C P Mendonça1, Milo Malanga2
1Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork T12 YN60, Ireland.
International journal of pharmaceutics
|December 21, 2024
概括
环极素 (CDs) 的结构修改增强了它们用于治疗小干扰RNA (siRNA) 传递的潜力. 在细胞模型中,使用特定氨基群的功能化CD显著提高了基因沉默的有效性.
科学领域:
- 生物材料科学 生物材料科学
- 药用化学 医学化学
- 纳米技术 纳米技术
背景情况:
- 环极素 (CDs) 具有基组,使其能够用于治疗应用.
- 对于小干扰RNA (siRNA) 输送系统,正在探索电离子两性CD.
研究的目的:
- 为增强siRNA传递合成和评估电离性两性循环德克斯特林.
- 建立结构-活性关系,以优化基因沉默功效.
主要方法:
- 合成各种具有不同氨基功能和链接器的化两性β-和γ-环氧素.
- 制备循环德克斯特林-siRNA纳米粒子 (NP) 并评估它们的物理化学特性.
- 在A549-luc细胞中使用 luciferase 记者基因进行基因沉默功效的体外评估.
主要成果:
- 与C2位置的三级氨基相比,与初级氨基修饰相比,基因沉默率更高.
- 在C2和C3位置使用氨基群的功能化进一步改善了基因表达抑制.
- 一种在g-CD上具有双重初级氨基功能的硫烯连接剂,可实现高达80%的基因淘汰.
结论:
- 循环德克斯特林的特定结构修改显著增强siRNA传递和基因沉默.
- 胺功能的类型和位置,以及链接器,对于优化生物材料性能至关重要.
- 这项研究确定了开发有效的循环德素基siRNA疗法的关键结构特征.
更多相关视频
15:55Long-term Silencing of Intersectin-1s in Mouse Lungs by Repeated Delivery of a Specific siRNA via Cationic Liposomes. Evaluation of Knockdown Effects by Electron Microscopy
Published on: June 21, 2013
10.6K
08:31Porous Silicon Microparticles for Delivery of siRNA Therapeutics
Published on: January 15, 2015
10.9K
相关概念视频
02:30siRNA - Small Interfering RNAs
16.6K
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...
16.6K
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