Issue 42, 2017

Efficient liposome fusion mediated by lipid–nucleic acid conjugates

Abstract

The fusion of biomembranes with release of encapsulated content in a controlled way is crucial for cell signaling, endo- and exocytosis and intracellular trafficking. Programmable fusion of liposomes and an efficient mixing of their contents have the potential to enable the study of chemical and enzymatic processes in a confined environment and under crowded conditions outside biological systems. We report on DNA-controlled fusion of lipid bilayer membranes using lipid–nucleic acid conjugates (LiNAs) to mediate lipid and content mixing of liposomes. Screening of different membrane anchor and linker structures as well as incubation temperatures led to significantly improved fusion and content mixing compared to reported systems. LiNA designs were optimized by changing lipophilic moieties as membrane anchors, PEG-spacer patterns and by introducing locked nucleic acid (LNA) modifications. Liposome fusion induced by complementary LiNAs results in remarkable efficient content mixing at 37 °C and 50 °C (up to 70%) with low leakage (≤5%).

Graphical abstract: Efficient liposome fusion mediated by lipid–nucleic acid conjugates

Supplementary files

Article information

Article type
Paper
Submitted
04 Aug 2017
Accepted
09 Okt 2017
First published
09 Okt 2017

Org. Biomol. Chem., 2017,15, 8936-8945

Efficient liposome fusion mediated by lipid–nucleic acid conjugates

O. Ries, P. M. G. Löffler, A. Rabe, J. J. Malavan and S. Vogel, Org. Biomol. Chem., 2017, 15, 8936 DOI: 10.1039/C7OB01939D

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