由双胞胎表面活性剂介导的转染:从内分体隔间的工程逃逸
Paul C Bell1, Mark Bergsma, Igor P Dolbnya
1Contribution from the Physical Organic Chemistry Unit, Stratingh Institute, University of Groningen, 4 Nijenborgh, 9747 AG Groningen, The Netherlands.
Journal of the American Chemical Society
|February 6, 2003
概括
基于糖的双子座表面活性剂1形成独特的脂质复合结构. 一个pH诱导的转移到一个倒置的六角相增强基因传递通过破坏内分泌体DNA释放.
科学领域:
- 生物物理化学 生物物理化学
- 材料科学 材料科学 材料科学
- 基因传递系统是基因传递系统.
背景情况:
- 由DNA和阴离子表面活性剂形成的脂质复合体对于基因传递至关重要.
- 了解唇形态是优化传染效率的关键.
- 基于糖的双子座表面活性剂提供了改进基因传递载体的潜力.
研究的目的:
- 为了研究DNA/双子表面活性剂1的结构变化,在pH范围内进行脂质复合.
- 为了将脂积体形态与表面活性剂结构和传染效率相关联.
- 阐明pH诱导的基因释放的机制,这种释放由双子座表面活性剂促进 1.
主要方法:
- 微角X射线散射 (SAXS) 用于分析唇结构.
- 电子显微镜 (cryo-TEM) 用于对形态的高分辨率成像.
- 分子建模以将表面活性剂特征与观察到的结构联系起来.
主要成果:
- 观察到三种不同的唇形态:片状,凝结片状和倒立六角形 (H ((II)) 阶段.
- 确定了影响形态的关键表面活性特征 (间隙长度,可发射的,不和尾巴,糖头组).
- 在内体pH时,已证明pH诱导的过渡到H (II) 阶段.
结论:
- 双子座表面活性剂1形成pH响应的脂质复合体,具有可调整的形态.
- 在内体pH值过渡到H(II) 阶段,促进了内体不稳定和DNA释放.
- 这种pH触发机制解释了双子座表面活性剂1在基因传递方面的高转染效率.
相关概念视频
01:28The Early Endosome: Endocytosis of Transferrin
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
00:58Recycling Endosomes and Transcytosis
The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
01:19Membrane Asymmetry Regulating Transporters
Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
01:15Transcytosis of IgG
Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
01:23Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport
Drugs need to permeate cell membranes to reach their target sites after administration. Orally administered drugs must transcend intestinal epithelial membrane barriers to infiltrate the systemic circulation. Drugs with a molecular weight of less than 500 Daltons diffuse through gaps between neighboring cells, called paracellular pathways.
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
01:06Carrier-Mediated Transport
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...