Delivery of Oligonucleotides to the Liver with GalNAc: From Research to Registered Therapeutic Drug. Oxford University Press is a department of the University of Oxford. and transmitted securely. Nucleic Acids Res.

It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. None of the tested ds 2'-F-modified PS-ONs caused DSBs, while the previously reported DSBs caused by ss 2'-F-modified PS-ONs were PS dependent. Bethesda, MD 20894, Web Policies 6).

Debacker AJ, Voutila J, Catley M, Blakey D, Habib N. Mol Ther. Importantly, asialoglycoprotein receptor-mediated uptake of N-acetylgalactosamine-conjugated ss or ds PS-ONs, even those with long PS stretches and high 2'-F content, was neither cytotoxic nor caused DSBs at transfection-equivalent exposures.

official website and that any information you provide is encrypted 2015 May 19;43(9):4569-78. doi: 10.1093/nar/gkv298.

is a recipient of a Marie Curie predoctoral fellowship. Clipboard, Search History, and several other advanced features are temporarily unavailable. Bookshelf We found that ss PS-ONs were more cytotoxic than double-stranded (ds) PS-ONs, irrespective of the 2'-ribose chemistry, inclusive of the 2'-F modification. The relatively mild cytotoxicity of ds ONs was most impacted by long contiguous PS stretches combined with 2'-F substitutions. Crooke ST, Baker BF, Xia S, Yu RZ, Viney NJ, Wang Y, Tsimikas S, Geary RS. 2018 Jun;28(3):119-127. doi: 10.1089/nat.2017.0709. 2019 Feb;29(1):16-32. doi: 10.1089/nat.2018.0753.

FOIA Epub 2018 Feb 9. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Cytotoxicity of ss ONs was most affected by the total PS content, with an additional contribution of 2'-F substitutions in HeLa, but not HepG2, cells. Epub 2018 Dec 20.

Discovery and preclinical evaluation of anti-miR-17 oligonucleotide RGLS4326 for the treatment of polycystic kidney disease. Dr Christine Nunn is also thanked for useful and interesting discussions. Your comment will be reviewed and published at the journal's discretion. Disclaimer, National Library of Medicine

However we have named it a triplet since it involves three DNA strands. Structure-function-dynamics relationships in the peculiar Planktothrix PCC7805 OCP1: Impact of his-tagging and carotenoid type. A nitrite-oxidising bacterium constitutively consumes atmospheric hydrogen.

2'-Fluoro-modified phosphorothioate oligonucleotide can cause rapid degradation of P54nrb and PSF. HeLa cells were more sensitive to ON-mediated toxicity when transfected with Lipofectamine 2000 versus Lipofectamine RNAiMax. 2017 Mar 17;45(5):2294-2306. doi: 10.1093/nar/gkx060. MeSH In any case, it is not surprising that C31 is partially disordered since there are no hydrophobic interactions with neighbour bases which might further stabilize its conformation. Departament d'Enginyeria Qumica, Universitat Politcnica de Catalunya. Nucleic Acids Res.

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T triplet in which the cytosine forms two hydrogen bonds with adenine A26 in a way similar to a reverse Hoogsteen interaction (Fig. Copyright 2022 Oxford University Press. Nucleic Acid Ther. Nucleic Acid Ther. N.G.A.A. 2020 Aug 20;48(14):7623-7639. doi: 10.1093/nar/gkaa576. Signal Transduct Target Ther. An official website of the United States government.

Detzer A, Overhoff M, Mescalchin A, Rompf M, Sczakiel G. Curr Pharm Des.

Phosphorothioate-stimulated cellular uptake of siRNA: a cell culture model for mechanistic studies. Miller CM, Tanowitz M, Donner AJ, Prakash TP, Swayze EE, Harris EN, Seth PP. Epub 2015 Apr 8. sharing sensitive information, make sure youre on a federal Schmidt K, Prakash TP, Donner AJ, Kinberger GA, Gaus HJ, Low A, stergaard ME, Bell M, Swayze EE, Seth PP. The site is secure. Hydrolysis of norfloxacin in the hyporheic zone: kinetics and pathways. 2-fluoro; antisense; cytotoxicity; oligonucleotide; phosphorothioate; siRNA. Single-stranded (ss) 2'-fluoro (2'-F)-modified oligonucleotides (ONs) with a full phosphorothioate (PS) backbone have been reported to be cytotoxic and cause DNA double-strand breaks (DSBs) when transfected into HeLa cells.

McIntosh CS, Aung-Htut MT, Fletcher S, Wilton SD. Characterizing the effect of GalNAc and phosphorothioate backbone on binding of antisense oligonucleotides to the asialoglycoprotein receptor. Hu B, Zhong L, Weng Y, Peng L, Huang Y, Zhao Y, Liang XJ. Would you like email updates of new search results? 2020 Aug 5;28(8):1759-1771. doi: 10.1016/j.ymthe.2020.06.015. A critical analysis of methods used to investigate the cellular uptake and subcellular localization of RNA therapeutics. Epub 2020 Jun 17. Receptor-Mediated Uptake of Phosphorothioate Antisense Oligonucleotides in Different Cell Types of the Liver. The .gov means its official. 2019 Sep 12;10(1):4148. doi: 10.1038/s41467-019-11918-y. Before Integrated Assessment of the Clinical Performance of GalNAc. Keywords: Careers. Search for other works by this author on: Unit de Chimie Organique, Institut Pasteur, The CRC Biomolecular Structure Unit, The Institute of Cancer Research. Nucleic Acids Res. Accessibility Int J Mol Sci. We are very grateful to Drs Valya Tereshko and Lourdes Campos for constant interest and help at various stages of this work. The https:// ensures that you are connecting to the

Unable to load your collection due to an error, Unable to load your delegates due to an error. 8600 Rockville Pike Thank you for submitting a comment on this article. LncRNA CTBP1-DT-encoded microprotein DDUP sustains DNA damage response signalling to trigger dual DNA repair mechanisms, Exploration of DNA processing features unravels novel properties of ICE conjugation in Gram-positive bacteria, Role of EXO1 nuclease activity in genome maintenance, the immune response and tumor suppression in, Cap-independent translation and a precisely located RNA sequence enable SARS-CoV-2 to control host translation and escape anti-viral response, Whole-genome long-read TAPS deciphers DNA methylation patterns at base resolution using PacBio SMRT sequencing technology, Chemical Biology and Nucleic Acid Chemistry, Gene Regulation, Chromatin and Epigenetics, Receive exclusive offers and updates from Oxford Academic, Crystallization and characterization of the thallium form of the, Hydrogen bond formation between the naturally modified nucleobase and phosphate backbone, Triplex hydration: nanosecond molecular dynamics simulation of the solvated triplex formed by mixed sequences, NMR solution structure of a parallel LNA quadruplex.

This work was supported by grant DGICYTPB93- 1067 and support from the Commissionat per Universitat i Recerca de la Generalitat de Catalunya. However, the molecular determinants of these effects have not been fully explored.

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T base pair, Three-dimensional structures of A-DNA, B-DNA and Z-DNA, NMR chemical shifts of the key residues observed in 1H NMR spectra of nucleic acid bases, NMR Chemical shifts of the key residues observed in 1H NMR spectra of the deoxyribose sugar in nucleic acids, Photograph of crystals of a DNA oligonucleotide, Techniques for determining nucleic acid structure, RNA has a hydroxyl group attached to the 2'-position of the sugar, and. This site needs JavaScript to work properly. These results suggest that in vitro cytotoxicity and DSBs associated with ONs are delivery method dependent and primarily determined by single-stranded nature and PS content of ONs.

government site. PMC thanks the British Council for partial support of his travel expenses at The Institute of Cancer Research. In this study, we investigated the impact of ON structure, chemistry, delivery method, and cell type on in vitro cytotoxicity and DSBs. 2019 Oct 31;20(21):5434. doi: 10.3390/ijms20215434. Federal government websites often end in .gov or .mil. N.G.A.A. An additional hydrogen bond is formed with A34 of the next base pair. Lee EC, Valencia T, Allerson C, Schairer A, Flaten A, Yheskel M, Kersjes K, Li J, Gatto S, Takhar M, Lockton S, Pavlicek A, Kim M, Chu T, Soriano R, Davis S, Androsavich JR, Sarwary S, Owen T, Kaplan J, Liu K, Jang G, Neben S, Bentley P, Wright T, Patel V. Nat Commun. 2020 Jun 19;5(1):101. doi: 10.1038/s41392-020-0207-x. Improving the valence self-reversible conversion of cerium nanoparticles on titanium implants by lanthanum doping to enhance ROS elimination and osteogenesis. Since C31 interacts with two adenines, it is obvious that the interaction is more complex than in conventional triple helices.