N6-methyl adenosine in siRNA evades immune response without reducing RNAi activity

Akihiro Imaeda; Fumiaki Tomoike; Mayu Hayakawa; Kosuke Nakamoto; Yasuaki Kimura; Naoko Abe; Hiroshi Abe

doi:10.1080/15257770.2019.1641205

N⁶-methyl adenosine in siRNA evades immune response without reducing RNAi activity

Nucleosides Nucleotides Nucleic Acids. 2019;38(12):972-979. doi: 10.1080/15257770.2019.1641205. Epub 2019 Jul 12.

Authors

Akihiro Imaeda¹, Fumiaki Tomoike², Mayu Hayakawa¹, Kosuke Nakamoto¹, Yasuaki Kimura¹, Naoko Abe¹, Hiroshi Abe^{1

3}

Affiliations

¹ Graduate School of Science, Nagoya University , Nagoya , Japan.
² Research Center for Materials Science, Nagoya University , Nagoya , Japan.
³ JST CREST, Science and Technology Agency , Tokyo , Japan.

PMID: 31298608
DOI: 10.1080/15257770.2019.1641205

Abstract

siRNA is a powerful method to suppress specific gene expression and has recently been utilized for molecular biology as well as medicine. However, introduction of dsRNA stimulates immune-responses as side-effects. In the present study, we utilized N⁶-methyl adenosine, one of the natural modified nucleosides, instead of adenosine in siRNA. When adenosine in the passenger or guide strand of siRNA was completely replaced with N⁶-methyl adenosine, the immune response against siRNA was evaded without any reduction in RNAi activity. This knowledge will promote the medical application of siRNA and enhance our understanding on cellular discrimination of non-self and self dsRNA.

Keywords: -methyl adenosine; immune-response; siRNA.

MeSH terms

Adenosine / analogs & derivatives*
Adenosine / chemistry
Base Sequence
Gene Expression
HeLa Cells
Humans
RNA Interference / immunology*
RNA, Double-Stranded / chemistry
RNA, Double-Stranded / metabolism
RNA, Small Interfering / chemistry*
RNA, Small Interfering / metabolism*

Substances

RNA, Double-Stranded
RNA, Small Interfering
N-methyladenosine
Adenosine