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Efficient Fusion of Liposomes by Nucleobase Quadruple-Anchored DNA

机译:通过核碱基锚定DNA高效融合脂质体

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摘要

Anchoring DNA via hydrophobic units into the membrane of vesicles allows tagging of these nanocontainers with sequence information. Moreover, the hybridization of DNA on the surface of liposomes enables sequence specific functionalization, vesicle aggregation, and vesicle fusion. Specifically, DNA-hybridization-based approaches for fusion employing oligonucleotides terminally modified with one or two anchoring units were hindered by a limited degree of full fusion or by significant leakage during fusion. The current work deals with a new strategy for anchoring oligonucleotides on a membrane by lipid-modified nucleobases rather than by attaching hydrophobic units to the 3'-or 5'-termini. The lipid anchors were incorporated into the DNA sequence via phosphoramidite nucleotide building blocks during automated solid-phase synthesis allowing variation of the number and position of hydrophobic units along the DNA backbone. Single-stranded DNA functionalized with four lipid-modified nucleobases was stably grafted onto the membrane of lipid vesicles. It was found that the orientation of DNA hybridization and the number of anchoring units play a crucial role in liposomal fusion, which in the most efficient system reached remarkable 29% content mixing without notable leakage.
机译:将DNA通过疏水单元锚固到囊泡的膜中,允许用序列信息标记这些纳米电池。此外,DNA在脂质体表面上的杂交能够使序列特异性官能化,囊泡聚集和囊泡融合。具体地,使用基于DNA杂交的融合方法,采用用一个或两个锚定单元的终止性改性的寡核苷酸终止于锚固单元的受损程度受到限制性的全融合或在融合过程中进行显着泄漏。目前的工作涉及通过脂质修饰的核碱基锚定寡核苷酸的新策略,而不是通过将疏水单元附着到3'-or 5'-末端。在自动固相合成期间通过磷酰胺嘧啶核苷酸构建块掺入DNA序列中的脂质锚,允许沿DNA主链的疏水单元的数量和位置的变化。用四种脂质改性的核碱基官能化的单链DNA被稳定地接枝到脂质囊泡的膜上。发现DNA杂交的取向和锚定单元的数量在脂质体融合中发挥着至关重要的作用,其在最有效的系统中,在没有显着泄漏的情况下达到显着的29%含量混合。

著录项

  • 来源
    《Chemistry: A European journal》 |2017年第39期|共6页
  • 作者单位

    Zernike Institute for Advanced Materials University of Groningen Nijenborgh 4 9747 AG Groningen (The Netherlands);

    Supramolecular &

    Biomaterials Chemistry Leiden Institute of Chemistry Leiden University P.O. Box 9502 2300 RA Leiden (The Netherlands);

    Zernike Institute for Advanced Materials University of Groningen Nijenborgh 4 9747 AG Groningen (The Netherlands);

    Zernike Institute for Advanced Materials University of Groningen Nijenborgh 4 9747 AG Groningen (The Netherlands);

    Zernike Institute for Advanced Materials University of Groningen Nijenborgh 4 9747 AG Groningen (The Netherlands);

    Zernike Institute for Advanced Materials University of Groningen Nijenborgh 4 9747 AG Groningen (The Netherlands);

    Zernike Institute for Advanced Materials University of Groningen Nijenborgh 4 9747 AG Groningen (The Netherlands);

    Supramolecular &

    Biomaterials Chemistry Leiden Institute of Chemistry Leiden University P.O. Box 9502 2300 RA Leiden (The Netherlands);

    Zernike Institute for Advanced Materials University of Groningen Nijenborgh 4 9747 AG Groningen (The Netherlands);

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 应用化学;
  • 关键词

    DNA hybridization; lipid-modified DNA; liposomes; vesicle fusion;

    机译:DNA杂交;脂质改性的DNA;脂质体;囊泡融合;

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