Skip global navigation and read the article

Skip global navigation and go to local navigation

Skip global navigation and go to footer navigation



Home  > Press Release  > Highly efficient silencing of microRNA by heteroduplex oligonucleotides.

Highly efficient silencing of microRNA by heteroduplex oligonucleotides.

Abstract

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.

Journal Article

JOURNAL:
Nucleic Acids Research

TITLE:
Highly efficient silencing of microRNA by heteroduplex oligonucleotides.

DOI:
https://doi.org/10.1093/nar/gkz492

Correspondence to

Takanori YOKOTA,M.D., Ph.D.,Professor
Department of Neurology and Neurological Science,
Graduate School of Medical and Dental Sciences,
Tokyo Medical and Dental University(TMDU)
E-mail:tak-yokota.nuro(at)tmd.ac.jp