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• W2018083537 abstract "Protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity of the 2'-O-(2-methoxy)ethyl (2'- MOE)-modified gapmer antisense oligonucleotide, ISIS113715, was previously reported. This antisense oligonucleotide increases insulin sensitivity and normalizes plasma glucose levels in diabetic ob/ob and db/db mice. In the present study, the isosequential 2'-O,4'-C-ethylene-bridged nucleic acid (ENA)-modified oligonucleotide, ENA-1, was synthesized, and its ability to further improve the downregulation of PTP1B in db/db mice was examined. We demonstrated that, compared with ISIS113715, intraperitoneal and subcutaneous administration of ENA-1 more effectively decreased the plasma glucose levels in db/db mice. Moreover, ENA-1 decreased expression of PTP1B in the liver and fat of db/db mice more effectively than ISIS113715. We describe for the first time the functional comparison of 2'-MOE- and ENA-modified antisense oligonucleotides. Our data indicate that the enhancement of the efficacy of antisense oligonucleotides by ENA modifications is superior to that of second-generation 2'-MOE modifications in certain aspects." @default.
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• W2018083537 date "2006-09-01" @default.
• W2018083537 modified "2023-10-15" @default.
• W2018083537 title "Direct Comparison of <i>In Vivo</i> Antisense Activity of ENA Oligonucleotides Targeting PTP1B mRNA with That of 2'-<i>O</i>-(2-Methoxy)ethyl-Modified Oligonucleotides" @default.
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• W2018083537 doi "https://doi.org/10.1089/oli.2006.16.253" @default.
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