Open AccessHighly efficient silencing of microRNA by heteroduplex oligonucleotides
Author(s) -
Koshiro Yoshioka,
Takehisa Kunieda,
Yasushi Asami,
Huijia Guo,
Haruka Miyata,
Kie Yoshida-Tanaka,
Yumiko Sujino,
Wenying Piao,
Hiroya Kuwahara,
Kazutaka Nishina,
Rintaro Iwata Hara,
Tetsuya Nagata,
Takehiko Wada,
Satoshi Obika,
Takanori Yokota
Publication year - 2019
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/gkz492
Subject(s) - oligonucleotide , biology , gene silencing , heteroduplex , microrna , in vivo , locked nucleic acid , rna interference , nucleic acid , microbiology and biotechnology , messenger rna , small interfering rna , rna , transfection , cell culture , genetics , dna , gene
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.