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Functionalized Acyclic (l)-Threoninol Nucleic Acid Four-Way Junction with High Stability In Vitro and In Vivo

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Oligonucleotides are increasingly being used as a programmable connection material to assemble molecules and proteins in well-defined structures. For the application of such assemblies for in vivo diagnostics or therapeutics it is crucial that the oligonucleotides form highly stable, non-toxic, and non-immunogenic structures. Only few oligonucleotide derivatives fulfil all of these requirements. Here we report on the application of acyclic l-threoninol nucleic acid (aTNA) to form a four-way junction (4WJ) that is highly stable and enables facile assembly of components for in vivo treatment and imaging. The aTNA 4WJ is serum-stable, shows no non-targeted uptake or cytotoxicity, and invokes no innate immune response. As a proof of concept, we modify the 4WJ with a cancer-targeting and a serum half-life extension moiety and show the effect of these functionalized 4WJs in vitro and in vivo, respectively.

Original languageEnglish
Article number202115275
JournalAngewandte Chemie - International Edition
Number of pages7
Publication statusPublished - Jun 2022

Bibliographical note

© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

    Research areas

  • aTNA, DNA, Holliday Junction, Nanostructures, CELLS, NANOBODIES, DNA NANOSTRUCTURES, PROTEINS, DELIVERY, Butylene Glycols, Nucleic Acids/chemistry, Oligonucleotides, RNA/chemistry, Amino Alcohols/chemistry, Nucleic Acid Conformation

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