在空气-液体界面培养的人类上皮肺细胞中提供纳米粒子介导的siRNA
Stina Rademacker1, Joschka T Müller1, Adrian P E Kromer1
1Department of Pharmacy, Pharmaceutical Technology and Biopharmacy, Ludwig-Maximilians-University Munich, Munich, Germany.
Methods in molecular biology (Clifton, N.J.)
|August 28, 2025
概括
空气-液体接口 (ALI) 模型提供先进的体外肺部模拟,用于评估肺部siRNA输送系统,包括脂质纳米粒子 (LNP) 和聚合物纳米粒子.
科学领域:
- 生物技术
- 纳米医学
- 肺部药物输送
背景情况:
- 第一个小干扰RNA (siRNA) 脂质纳米粒子 (LNP) 疗法于2018年获得批准,推进了siRNA疗法.
- 聚合 siRNA 输送系统 (多复合体,小复合体) 在可扩展性和适应性方面进行了研究.
- 肺部 siRNA 疗法在肝外输送方面面临挑战,需要先进的体外模型.
研究的目的:
- 为肺部siRNA输送研究提供空气液体接口 (ALI) 模型的概述.
- 突出ALI模型适用于高通量查和3R原则的遵守.
- 讨论ALI模型在评估纳米粒子吸收和基因淘汰中的应用.
主要方法:
- 建立和培养ALI细胞培养模型.
- 基于显微镜的ALI模型生理特征.
- 使用ALI模型对聚合物纳米粒子和LNP进行体外评估.
主要成果:
- ALI模型复制了肺部的关键生理特征,
- 这些模型适用于肺输送系统的体外研究.
- 应用包括评估纳米粒子吸收和基因淘汰效率.
结论:
- ALI模型对于推进肺部siRNA输送研究至关重要.
- 它们可以有效地对纳米粒子配方进行体外选.
- 这些模型支持开发新型的肝外siRNA疗法.
相关概念视频
RNA 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...
siRNA - 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...
piRNA - Piwi-interacting RNAs
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...
Experimental 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...
Small interfering RNAs (siRNA)
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...


