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Highly efficient silencing of microRNA by heteroduplex oligonucleotides.
Yoshioka, Kotaro; Kunieda, Taiki; Asami, Yutaro; Guo, Huijia; Miyata, Haruka; Yoshida-Tanaka, Kie; Sujino, Yumiko; Piao, Wenying; Kuwahara, Hiroya; Nishina, Kazutaka; Hara, Rintaro Iwata; Nagata, Tetsuya; Wada, Takeshi; Obika, Satoshi; Yokota, Takanori.
Affiliation
  • Yoshioka K; Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences and Center for Brain Integration Research, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
  • Kunieda T; Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
  • Asami Y; Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences and Center for Brain Integration Research, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
  • Guo H; Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
  • Miyata H; Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences and Center for Brain Integration Research, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
  • Yoshida-Tanaka K; Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
  • Sujino Y; Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences and Center for Brain Integration Research, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
  • Piao W; Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences and Center for Brain Integration Research, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
  • Kuwahara H; Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
  • Nishina K; Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences and Center for Brain Integration Research, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
  • Hara RI; Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
  • Nagata T; Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences and Center for Brain Integration Research, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
  • Wada T; Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
  • Obika S; Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences and Center for Brain Integration Research, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
  • Yokota T; Section of Molecular Technology, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
Nucleic Acids Res ; 47(14): 7321-7332, 2019 08 22.
Article in En | MEDLINE | ID: mdl-31214713
AntimiR is an antisense oligonucleotide that has been developed to silence microRNA (miRNA) for the treatment of intractable diseases. Enhancement of its in vivo efficacy and improvement of its toxicity are highly desirable but remain challenging. We here design heteroduplex oligonucleotide (HDO)-antimiR as a new technology comprising an antimiR and its complementary RNA. HDO-antimiR binds targeted miRNA in vivo more efficiently by 12-fold than the parent single-stranded antimiR. HDO-antimiR also produced enhanced phenotypic effects in mice with upregulated expression of miRNA-targeting messenger RNAs. In addition, we demonstrated that the enhanced potency of HDO-antimiR was not explained by its bio-stability or delivery to the targeted cell, but reflected an improved intracellular potency. Our findings provide new insights into biology of miRNA silencing by double-stranded oligonucleotides and support the in vivo potential of this technology based on a new class of for the treatment of miRNA-related diseases.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA, Single-Stranded / Oligonucleotides, Antisense / Gene Silencing / MicroRNAs / Nucleic Acid Heteroduplexes Limits: Animals Language: En Journal: Nucleic Acids Res Year: 2019 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA, Single-Stranded / Oligonucleotides, Antisense / Gene Silencing / MicroRNAs / Nucleic Acid Heteroduplexes Limits: Animals Language: En Journal: Nucleic Acids Res Year: 2019 Document type: Article