@article{106384da4483454881a56b870816204a,
title = "Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency",
abstract = "The design of modified oligonucleotides that combine in one molecule several therapeutically beneficial properties still poses a major challenge. Recently a new type of modified mesyl phosphoramidate (or μ-) oligonucleotide was described that demonstrates high affinity to RNA, exceptional nuclease resistance, efficient recruitment of RNase H, and potent inhibition of key carcinogenesis processes in vitro. Herein, using a xenograft mouse tumor model, it was demonstrated that microRNA miR-21-targeted μ-oligonucleotides administered in complex with folate-containing liposomes dramatically inhibit primary tumor growth via long-term down-regulation of miR-21 in tumors and increase in biosynthesis of miR-21-regulated tumor suppressor proteins. This antitumoral effect is superior to the effect of the corresponding phosphorothioate. Peritumoral administration of μ-oligonucleotide results in its rapid distribution and efficient accumulation in the tumor. Blood biochemistry and morphometric studies of internal organs revealed no pronounced toxicity of μ-oligonucleotides. This new oligonucleotide class provides a powerful tool for antisense technology.",
keywords = "Antisense oligonucleotide, DNA modification, Mesyl oligonucleotide, Oncogenic microRNA, Phosphorothioate, HEPATOCYTES, oncogenic microRNA, TRAFFICKING, PROLIFERATION, TOXICITY, CELLULAR UPTAKE, NUCLEIC-ACIDS, DELIVERY, antisense oligonucleotide, phosphorothioate, SIGNALING PATHWAY, mesyl oligonucleotide, HEPATOTOXICITY, DERIVATIVES",
author = "Patutina, {Olga A.} and Gaponova, {Svetlana K.} and Sen'kova, {Aleksandra V.} and Savin, {Innokenty A.} and Gladkikh, {Daniil V.} and Burakova, {Ekaterine A.} and Fokina, {Alesya A.} and Maslov, {Mikhail A.} and Shmendel', {Elena V.} and Wood, {Mattew J.A.} and Vlassov, {Valentin V.} and Sidney Altman and Stetsenko, {Dmitry A.} and Zenkova, {Marina A.}",
note = "Funding Information: ACKNOWLEDGMENTS. This work was funded by Russian Science Foundation Grant 19-74-30011, the Russian State-funded budget project of Institute of Chemical Biology and Fundamental Medicine SB RAS Grant AAAA-A17-117020210024-8, and Russian Foundation for Basic Research Grants 18-515-05007 and 18-515-57006. We thank Dr. B. P. Chelobanov for synthesis of Cy5.5-labeled oligonucleotides. Publisher Copyright: {\textcopyright} 2020 mSystems. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = dec,
day = "22",
doi = "10.1073/pnas.2016158117",
language = "English",
volume = "117",
pages = "32370--32379",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "51",
}