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


Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
13 06 2022
Historique:
received: 10 11 2021
pubmed: 31 3 2022
medline: 31 5 2022
entrez: 30 3 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 35352451
doi: 10.1002/anie.202115275
pmc: PMC9324938
doi:

Substances chimiques

Amino Alcohols 0
Butylene Glycols 0
Nucleic Acids 0
Oligonucleotides 0
threoninol 0
RNA 63231-63-0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202115275

Informations de copyright

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

Références

Adv Sci (Weinh). 2019 Nov 23;7(2):1900973
pubmed: 31993277
Chem Commun (Camb). 2015 Apr 18;51(30):6500-3
pubmed: 25633432
Org Biomol Chem. 2016 Feb 7;14(5):1540-4
pubmed: 26731694
J Am Chem Soc. 2010 Oct 27;132(42):14702-3
pubmed: 20886877
J Control Release. 2016 Oct 10;239:27-38
pubmed: 27527555
Chemistry. 2019 Sep 20;25(53):12303-12307
pubmed: 31373735
Angew Chem Int Ed Engl. 2008;47(12):2253-5
pubmed: 18275058
ACS Nano. 2014 Jul 22;8(7):6633-43
pubmed: 24963790
Nat Commun. 2017 Jul 17;8:16092
pubmed: 28714475
Bioorg Med Chem Lett. 2002 Oct 21;12(20):2883-6
pubmed: 12270169
Pharm Res. 2012 Aug;29(8):2104-14
pubmed: 22485010
J Biol Chem. 2017 Aug 11;292(32):13312-13322
pubmed: 28637874
J Am Chem Soc. 2013 Jan 9;135(1):340-6
pubmed: 23210862
Mol Imaging. 2018 Jan-Dec;17:1536012117745386
pubmed: 29357745
J Am Chem Soc. 2008 May 7;130(18):5846-7
pubmed: 18407636
Nat Chem. 2014 Sep;6(9):804-9
pubmed: 25143216
Angew Chem Int Ed Engl. 2022 Jun 13;61(24):e202115275
pubmed: 35352451
FASEB J. 2011 Jul;25(7):2433-46
pubmed: 21478264
Org Biomol Chem. 2019 Sep 7;17(33):7655-7659
pubmed: 31360984
ACS Appl Mater Interfaces. 2016 Feb;8(7):4378-84
pubmed: 26878704
Nucleic Acids Res. 1999 Dec 15;27(24):4801-6
pubmed: 10572181
Int J Mol Sci. 2019 Mar 05;20(5):
pubmed: 30841523
Theranostics. 2019 Apr 13;9(9):2662-2677
pubmed: 31131060
Angew Chem Int Ed Engl. 2013 Dec 23;52(52):14080-3
pubmed: 24353230
Chembiochem. 2019 Apr 15;20(8):1014-1018
pubmed: 30589193
EBioMedicine. 2016 Jun;8:40-48
pubmed: 27428417
J Am Chem Soc. 2014 Aug 6;136(31):10850-3
pubmed: 25029632
Small. 2016 Oct;12(40):5601-5611
pubmed: 27571230
Org Biomol Chem. 2015 Feb 28;13(8):2366-74
pubmed: 25564220

Auteurs

Anders Märcher (A)

Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.

Vipin Kumar (V)

Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.

Veronica L Andersen (VL)

Department of Molecular Biology and Genetics, and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.

Kassem El-Chami (K)

Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.

Thuy J D Nguyen (TJD)

Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.

Mads K Skaanning (MK)

Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.

Imke Rudnik-Jansen (I)

Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.

Jesper S Nielsen (JS)

Department of Molecular Biology and Genetics, and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.

Kenneth A Howard (KA)

Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.

Jørgen Kjems (J)

Department of Molecular Biology and Genetics, and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.

Kurt V Gothelf (KV)

Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.

Articles similaires

Humans RNA, Circular Exosomes Cell Proliferation Epithelial-Mesenchymal Transition
DNA Methylation Humans DNA Animals Machine Learning
Cryoelectron Microscopy Models, Molecular RNA DNA Nucleic Acid Conformation
Crystallography, X-Ray DNA Protein Binding HMGA Proteins AT-Hook Motifs

Classifications MeSH