Open Access
Proceedings of the National Academy of Sciences of the United States of America, volume 117, issue 51, pages 32370-32379
Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency
Patutina Olga A
1
,
Gaponova (miroshnichenko) Svetlana K
1
,
Senkova Aleksandra V
1
,
Savin Innokenty A
1
,
Gladkikh Daniil V.
1
,
Burakova Ekaterine A
2, 3
,
Fokina Alesya A.
2, 3
,
Maslov Michael
4
,
Shmendel Elena V
4
,
Wood Mattew J A
5
,
Vlassov Valentin V
1
,
Altman Sidney
6, 7
,
Stetsenko Dmitry A.
2, 3
,
Zenkova Marina A
1
7
Life Sciences Division, Arizona State University, Tempe, AZ 85287-4501
|
Publication type: Journal Article
Publication date: 2020-12-22
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 11.1
ISSN: 00278424, 10916490
PubMed ID:
33288723
Multidisciplinary
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.
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1 publication, 3.33%
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1 publication, 3.33%
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1 publication, 3.33%
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1 publication, 3.33%
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1 publication, 3.33%
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Citations by publishers
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1 publication, 3.33%
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American Chemical Society (ACS)
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American Chemical Society (ACS)
1 publication, 3.33%
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Frontiers Media S.A.
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Frontiers Media S.A.
1 publication, 3.33%
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Patutina O. A. 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. Vol. 117. No. 51. pp. 32370-32379.
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Patutina O. A., Gaponova (miroshnichenko) S. K., Senkova A. V., Savin I. A., Gladkikh D. V., Burakova E. A., Fokina A. A., Maslov M., Shmendel E. V., Wood M. J. A., Vlassov V. V., Altman S., Stetsenko D. A., Zenkova M. A. 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. Vol. 117. No. 51. pp. 32370-32379.
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TY - JOUR
DO - 10.1073/pnas.2016158117
UR - https://doi.org/10.1073%2Fpnas.2016158117
TI - Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency
T2 - Proceedings of the National Academy of Sciences of the United States of America
AU - Patutina, Olga A
AU - Gaponova (miroshnichenko), Svetlana K
AU - Senkova, Aleksandra V
AU - Gladkikh, Daniil V.
AU - Burakova, Ekaterine A
AU - Fokina, Alesya A.
AU - Maslov, Michael
AU - Wood, Mattew J A
AU - Vlassov, Valentin V
AU - Altman, Sidney
AU - Stetsenko, Dmitry A.
AU - Zenkova, Marina A
AU - Savin, Innokenty A
AU - Shmendel, Elena V
PY - 2020
DA - 2020/12/22 00:00:00
PB - Proceedings of the National Academy of Sciences (PNAS)
SP - 32370-32379
IS - 51
VL - 117
PMID - 33288723
SN - 0027-8424
SN - 1091-6490
ER -
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@article{2020_Patutina,
author = {Olga A Patutina and Svetlana K Gaponova (miroshnichenko) and Aleksandra V Senkova and Daniil V. Gladkikh and Ekaterine A Burakova and Alesya A. Fokina and Michael Maslov and Mattew J A Wood and Valentin V Vlassov and Sidney Altman and Dmitry A. Stetsenko and Marina A Zenkova and Innokenty A Savin and Elena V Shmendel},
title = {Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2020},
volume = {117},
publisher = {Proceedings of the National Academy of Sciences (PNAS)},
month = {dec},
url = {https://doi.org/10.1073%2Fpnas.2016158117},
number = {51},
pages = {32370--32379},
doi = {10.1073/pnas.2016158117}
}
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Patutina, Olga A., 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, vol. 117, no. 51, Dec. 2020, pp. 32370-32379. https://doi.org/10.1073%2Fpnas.2016158117.
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