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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.<\/jats:p>","DOI":"10.1093\/nar\/gkz492","type":"journal-article","created":{"date-parts":[[2019,5,28]],"date-time":"2019-05-28T19:14:54Z","timestamp":1559070894000},"page":"7321-7332","source":"Crossref","is-referenced-by-count":41,"title":["Highly efficient silencing of microRNA by heteroduplex oligonucleotides"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7094-9017","authenticated-orcid":false,"given":"Kotaro","family":"Yoshioka","sequence":"first","affiliation":[{"name":"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"},{"name":"Section of 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