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

Autor: Märcher A; Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark., Kumar V; Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark., Andersen VL; Department of Molecular Biology and Genetics, and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark., El-Chami K; Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark., Nguyen TJD; Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark., Skaanning MK; Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark., Rudnik-Jansen I; Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark., Nielsen JS; Department of Molecular Biology and Genetics, and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark., Howard KA; Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark., Kjems J; Department of Molecular Biology and Genetics, and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark., Gothelf KV; Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2022 Jun 13; Vol. 61 (24), pp. e202115275. Date of Electronic Publication: 2022 Apr 13.
DOI: 10.1002/anie.202115275
Abstrakt: 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.
(© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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