悬挂聚合物:阿米诺-β-环极:siRNA 客:宿主纳米粒子作为基因沉默的有效载体
Aditya Kulkarni1, Kyle DeFrees, Seok-Hee Hyun
1Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA.
Journal of the American Chemical Society
|May 2, 2012
概括
一个新的自组装纳米粒子系统有效地提供siRNA. 这种新型载体由阴离子β-cyclopodextrin和可降解的聚合物制成,具有较低的毒性和与现有方法相比的基因沉默.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术纳米技术
- 基因传递 基因传递
背景情况:
- 开发安全有效的siRNA传递载体对于基因治疗至关重要.
- 现有的非病毒载体经常面临毒性和效率方面的挑战.
- 自组装纳米材料为向药物和核酸输送提供了一个有前途的平台.
研究的目的:
- 开发和描述一种用于siRNA输送的新型自组装纳米粒子系统.
- 评估开发的载体的效率和细胞毒性.
- 将新型载体的性能与基准转染试剂进行比较.
主要方法:
- 合成单位置换的阳离子β-环氧德克斯特林衍生物.
- 用聚乙烯醇 (PVA) 与聚乙烯基醇 (PEG) 和胆固醇 (Chol) 接种物通过酸-性链接制备.
- 使用两个自组装方案与siRNA.RNA一起研究纳米粒子形成.
- 纳米粒子大小和泽塔潜力的表征.
- 在CHO-GFP细胞中评估细胞活力和基因沉默效率.
主要成果:
- 电离β-CD衍生物和Chol-PVA-PEG聚合物形成的纳米粒子 (120-170nm) 与siRNA的自组合.
- 纳米粒子表现出轻微负的泽塔潜力.
- 与25 kDa bPEI相比,新型载体的细胞毒性降低了1000倍.
- 基因沉默效率与bPEI和Lipofectamine 2000等基准试剂的效率相当.
结论:
- 开发的自组装系统有效地形成了用于siRNA传递的纳米粒子.
- 这种新型载体为基因沉默应用提供了低毒性的替代方案.
- 这种方法有可能推进非病毒siRNA疗法.
相关概念视频
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...
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...
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...
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...
Site-Targeted Drug Delivery Systems: Polymeric Carriers
Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...


