Design, synthesis and membrane anchoring strength of lipidated polyaza crown ether DNA-conjugates (LiNAs) studied by DNA-controlled assembly of liposomes

Abstract

Hybridization-controlled assays for assembly or fusion of liposomes are versatile for detection of both DNA and RNA targets and useful for the evaluation of membrane anchoring strength of LiNAs with applications in the context of liposome assembly, liposome fusion and lipid nanoparticle formulation of therapeutic LiNAs. Herein, we report the synthesis of lipid phosphoramidite building blocks for automated LiNA synthesis and a study on design requirements for efficient lipid membrane anchoring and liposome assembly dependent on lipid membrane anchor length (C₁₀-C₂₀) and structure, the effect of internal linkers and locked nucleic acids (LNA) building blocks on the lipid membrane anchoring strength of LiNAs.