Efficient Fusion of Liposomes by Nucleobase Quadruple-Anchored DNA,Chemistry - A European Journal

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Efficient Fusion of Liposomes by Nucleobase Quadruple-Anchored DNA
Chemistry - A European Journal ( IF 3.9 ) Pub Date : 2017-06-20 06:46:12 , DOI: 10.1002/chem.201701379
Zhuojun Meng ₁ , Jian Yang ₂ , Qing Liu ₁ , Jan Willem de Vries ₁ , Agnieszka Gruszka ₁ , Alberto Rodríguez-Pulido ₁ , Bart J. Crielaard _{1,

3} , Alexander Kros ₂ , Andreas Herrmann _{1,

3}

Affiliation

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.

中文翻译：

核碱基四锚定DNA对脂质体的有效融合

通过疏水单元将DNA锚定在囊泡膜中，可以用序列信息标记这些纳米容器。而且，脂质体表面上DNA的杂交使得序列特异性功能化，囊泡聚集和囊泡融合成为可能。具体地，有限度的完全融合或融合过程中的显着渗漏阻碍了基于DNA杂交的基于融合方法的应用，所述方法使用用一个或两个锚定单元末端修饰的寡核苷酸进行融合。当前的工作涉及通过脂质修饰的核碱基而不是通过将疏水单元连接到3'-或5'-末端将寡核苷酸锚定在膜上的新策略。在自动固相合成过程中，脂质锚定物通过亚磷酰胺核苷酸构建基团掺入DNA序列中，从而可沿DNA主链改变疏水单元的数量和位置。用四个脂质修饰的核碱基功能化的单链DNA稳定移植到脂质囊泡的膜上。结果发现，DNA杂交的方向和锚定单元的数量在脂质体融合中起着至关重要的作用，在最有效的系统中，脂质体的混合含量达到了29％，而没有明显的泄漏。

更新日期：2017-06-21

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