In vivo antisense activity of ENA oligonucleotides targeting PTP1B mRNA in comparison of that of 2'-MOE-modified oligonucleotides.

In vivo antisense activity of ENA oligonucleotides targeting PTP1B mRNA in comparison of that of 2'-MOE-modified oligonucleotides. Research Abstract Details 

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In vivo antisense activity of ENA oligonucleotides targeting PTP1B mRNA in comparison of that of 2'-MOE-modified oligonucleotides. Abstract Text:

Makoto Koizumi,Miho Takagi-Sato,Ryo Okuyama,Kazushi Araki,Weiyong Sun,Daisuke Nakai,

The 2'-0-(2-methoxy)ethyl (2'-MOE)-modified gapmer antisense oligonucleotide ISIS113715, which targets protein-tyrosine phosphatase IB (PTP1B) mRNA, increases insulin sensitivity and normalizes plasma glucose levels in diabetic ob/ob and db/db mice. In the present study, the efficacy of the isosequential 2'-O,4'-C-ethylene-bridged nucleic acid (ENA)-modified oligonucleotide ENA-1 was compared with that of ISIS113715 in order to further improve the down-regulation of PTP1B in db/db mice. Intraperitoneal administration of ENA-1 more effectively decreased the plasma glucose levels in db/db mice than ISIS113715. Moreover, ENA-1 decreased the expression of PTP1B in the liver and fat of db/db mice more effectively than ISIS113715. These data indicate that ENA modifications enhance the ability of antisense oligonucleotides and make them superior to second-generation 2'-MOE modifications. We would like to thank to Drs. Shinya Tsutsumi and Kenji Kawai for the T(m) measurement and autoradiography experiments. ENA is a registered trademark of Mitsubishi-Kagaku Foods Corporation.

In vivo antisense activity of ENA oligonucleotides targeting PTP1B mRNA in comparison of that of 2'-MOE-modified oligonucleotides. Publishing Authors By Initials

M Koizumi,M Takagi-Sato,R Okuyama,K Araki,W Sun,D Nakai,

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In vivo antisense activity of ENA oligonucleotides targeting PTP1B mRNA in comparison of that of 2'-MOE-modified oligonucleotides. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Nucleic acids symposium series (2004)

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Page Numbers: 111-2

Journal Abbreviation: Nucleic Acids Symp Ser (Oxf)

ISSN: 1746-8272

DAY: 21

MONTH: 11

YEAR: 2007

In vivo antisense activity of ENA oligonucleotides targeting PTP1B mRNA in comparison of that of 2'-MOE-modified oligonucleotides. Information

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LANGUAGE: eng

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Grant and Affiliation Information for In vivo antisense activity of ENA oligonucleotides targeting PTP1B mRNA in comparison of that of 2'-MOE-modified oligonucleotides.

AFFILIATION: Advanced Technology Research Laboratories, R&D Planning Department, Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi-Sankyo Co., Ltd. 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. koizumi.makoto.h7@daiichisankyo.co.jp

Country: England

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MEDLINETA: Nucleic Acids Symp Ser (Oxf)

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