To meet the criteria for efficient delivery,the cationic amphiphile system condenses the reporter-DNA by displacement of the positively charged(inorganic)counterions and,after binding,'transports'the so-formed lipoplex to the cell surface.During thes
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To meet the criteria for efficient delivery,the cationic amphiphile system condenses the reporter-DNA by displacement of the positively charged(inorganic)counterions and,after binding,'transports'the so-formed lipoplex to the cell surface.During thes
To meet the criteria for efficient delivery,the cationic amphiphile system condenses the reporter-DNA by displacement of the positively charged(inorganic)counterions and,after binding,'transports'the so-formed lipoplex to the cell surface.During these stages,DNA protection and preservation of the lipoplex morphology are important issues.After reaching the cell surface,interaction of the positively charged lipoplex with the negatively charged plasma membrane of the cell is facilitated,initiating the membrane transfer processes.The subsequent passage across the cell membrane and escape of the DNA materail into the cytoplasm finalize the first part of this trajectory.Endocytosis positively influences this part of the sequence,which involves the release of DNA from the endosomal compartment,facilitated by an as yet largely unresolved mechanism of disruption of the endosomal membrane.stages in the pathway clearly benefit from radically different types of morphological behavior of the lipoplex and the constituting lipids.
A potential method of improving the delivery capabilities of synthetic bilayer-forming amphiphiles is to induce a morphological change of the lipoplex from a relative stable lamellar phase(DNA condensing morphology)into an inverted hexagonal phase(H11),recognized as the most effective morphology for in vitro transfection.The hexagonal phase morphology does not necessarily facilitate the interaction with the cell membrane but appears pivotal for the escape from the endosomal compartment.Preferably,the morphological changes are only induced in the proximity of or after contact with the cell membrane or,alternatively,at the endosomal level.This rational has been applied to the design of novel cytofectins,the so-called Sunfish amphiphiles(Scheme 1),by attaching a flexible"antenna"to the cationic headgroup rather than a methyl moiety,as in the structurally related SAINT amphiphiles 2.
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To meet the criteria for efficient delivery,the cationic amphiphile system condenses the reporter-DNA by displacement of the positively charged(inorganic)counterions and,after binding,'transports'the so-formed lipoplex to the cell surface.During thes
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To meet the criteria for efficient delivery,the cationic amphiphile system condenses the reporter-DNA by displacement of the positively charged(inorganic)counterions and,after binding,'transports'the so-formed lipoplex to the cell surface. During these stages,DNA protection and preservation of the lipoplex morphology are important issues. After reaching the cell surface,interaction of the positively charged lipoplex with the negatively charged plasma membrane of the cell is facilitated,initiating the membrane transfer processes. The subsequent passage across the cell membrane and escape of the DNA materail into the cytoplasm finalize the first part of this trajectory.
为符合有效传递的评价标准,处理阳离子两亲化合物系统时,浓缩 reporter-DNA的方法是:经由带正电反离子的置换,在绑定后,将所形成的脂复合体传输到细胞表面.在这些过程中,关键问题在于如何实现DNA的保护与脂复合体形貌的维持.到达细胞表面,使得带正电的脂复合体与带负电质膜的相互作用易于进行,从而引发了膜传递过程.随后,跨越细胞膜的通道,以及细胞质中DNA的逃逸(?这句不很清楚),结束了这条路径的第一部分.
Endocytosis positively influences this part of the sequence,which involves the release of DNA from the endosomal compartment,facilitated by an as yet largely unresolved mechanism of disruption of the endosomal membrane. stages in the pathway clearly benefit from radically different types of morphological behavior of the lipoplex and the constituting lipids.
内吞作用促进了反应序列中的这一部分,其中包含DNA从内涵体腔中的释放.内涵体膜的分裂机理促进了这一过程,然而,关于此机理的本质尚未得到解释.很明显,此途径中的各阶段得益于脂复合体与所含脂质的形态学行为的类型的巨大差异.
A potential method of improving the delivery capabilities of synthetic bilayer-forming amphiphiles is to induce a morphological change of the lipoplex from a relative stable lamellar phase(DNA condensing morphology)into an inverted hexagonal phase(H11),recognized as the most effective morphology for in vitro transfection.
一条提高合成的双层两亲化合物传递能力的方法是,引发脂复合体的形态变化,从相对稳定的层状相(DNA凝聚态的形貌)转变为反转的六角相(H11),它(六角相)被公认为体外转染效率最高的形貌.
The hexagonal phase morphology does not necessarily facilitate the interaction with the cell membrane but appears pivotal for the escape from the endosomal compartment. Preferably,the morphological changes are only induced in the proximity of or after contact with the cell membrane or,alternatively,at the endosomal level.
六角相形貌并不能有效促进与细胞膜间的相互作用,但它对从内涵体腔中的逃逸起到关键作用.更令人感兴趣的是,形貌变化只在细胞膜的近邻处,或与细胞膜接触后,或在内涵体水平上引发.
This rational has been applied to the design of novel cytofectins,the so-called Sunfish amphiphiles(Scheme 1),by attaching a flexible"antenna"to the cationic headgroup rather than a methyl moiety,as in the structurally related SAINT amphiphiles
这种方式已被用于设计新型的细胞转染剂,即所谓的Sunfish两亲化合物(图解1).具体做法是,将阳离子头基接上一个柔韧的“触角”(而非像结构上与之类似的SAINT两亲化合物,后者的阳离子头基上所接基团为甲基).