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Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency. / Patutina, Olga A.; Gaponova, Svetlana K.; Sen'kova, Aleksandra V. et al.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 117, No. 51, 22.12.2020, p. 32370-32379.

Research output: Contribution to journal › Article › peer-review

Harvard

Patutina, OA, Gaponova, SK, Sen'kova, AV, Savin, IA, Gladkikh, DV, Burakova, EA, Fokina, AA, Maslov, MA, Shmendel', EV, Wood, MJA, Vlassov, VV, Altman, S, Stetsenko, DA & Zenkova, MA 2020, 'Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency', Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 51, pp. 32370-32379. https://doi.org/10.1073/pnas.2016158117

APA

Patutina, O. A., Gaponova, S. K., Sen'kova, A. V., Savin, I. A., Gladkikh, D. V., Burakova, E. A., Fokina, A. A., Maslov, M. A., Shmendel', E. V., Wood, M. J. A., Vlassov, V. V., Altman, S., Stetsenko, D. A., & Zenkova, M. A. (2020). Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency. Proceedings of the National Academy of Sciences of the United States of America, 117(51), 32370-32379. https://doi.org/10.1073/pnas.2016158117

Vancouver

Patutina OA, Gaponova SK, Sen'kova AV, Savin IA, Gladkikh DV, Burakova EA et al. Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency. Proceedings of the National Academy of Sciences of the United States of America. 2020 Dec 22;117(51):32370-32379. doi: 10.1073/pnas.2016158117

Author

Patutina, Olga A. ; Gaponova, Svetlana K. ; Sen'kova, Aleksandra V. et al. / Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency. In: Proceedings of the National Academy of Sciences of the United States of America. 2020 ; Vol. 117, No. 51. pp. 32370-32379.

BibTeX

@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",
publisher = "National Academy of Sciences",
number = "51",

}

RIS

TY - JOUR

T1 - Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency

AU - Patutina, Olga A.

AU - Gaponova, Svetlana K.

AU - Sen'kova, Aleksandra V.

AU - Savin, Innokenty A.

AU - Gladkikh, Daniil V.

AU - Burakova, Ekaterine A.

AU - Fokina, Alesya A.

AU - Maslov, Mikhail A.

AU - Shmendel', Elena V.

AU - Wood, Mattew J.A.

AU - Vlassov, Valentin V.

AU - Altman, Sidney

AU - Stetsenko, Dmitry A.

AU - Zenkova, Marina A.

N1 - 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: © 2020 mSystems. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/12/22

Y1 - 2020/12/22

N2 - 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.

AB - 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.

KW - Antisense oligonucleotide

KW - DNA modification

KW - Mesyl oligonucleotide

KW - Oncogenic microRNA

KW - Phosphorothioate

KW - HEPATOCYTES

KW - oncogenic microRNA

KW - TRAFFICKING

KW - PROLIFERATION

KW - TOXICITY

KW - CELLULAR UPTAKE

KW - NUCLEIC-ACIDS

KW - DELIVERY

KW - antisense oligonucleotide

KW - phosphorothioate

KW - SIGNALING PATHWAY

KW - mesyl oligonucleotide

KW - HEPATOTOXICITY

KW - DERIVATIVES

UR - http://www.scopus.com/inward/record.url?scp=85098207518&partnerID=8YFLogxK

U2 - 10.1073/pnas.2016158117

DO - 10.1073/pnas.2016158117

M3 - Article

C2 - 33288723

AN - SCOPUS:85098207518

VL - 117

SP - 32370

EP - 32379

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 51

ER -

ID: 27328879