Osaka University

Reiko Waki

Satoshi Obika

Yuya Kasahara

Tokuyuki Yoshida

Takao Inoue

Kunihiko Morihiro

Atsushi Mikami

Takao Yamaguchi

Masahiko Horiba

Yutaro Kotobuki

The present invention aims to provide an antisense oligonucleic acid with reduced hepatotoxicity. The antisense oligonucleic acid according to the present invention is characterized in that it has a base length of not less than 7 nt and not more than 30 nt, wherein nucleic acid residues of not less than 1 nt and not more than 5 nt respectively from the both terminals are 2',4′-bridged nucleic acids, 2′,4′-non-bridged nucleic acid residue(s) is(are) present between the above-mentioned both terminals, and one or more bases in the nucleic acid residue(s) of the above-mentioned 2′,4′-non-bridged nucleic acid residue(s) is/are modified.

Antisense oligonucleic acid

The present invention aims to provide an antisense oligonucleic acid with reduced hepatotoxicity. The antisense oligonucleic acid according to the present invention is characterized in that it has a base length of not less than 7 nt and not more than 30 nt, wherein nucleic acid residues of not less than 1 nt and not more than 5 nt respectively from the both terminals are 2',4&#x2032;-bridged nucleic acids, 2&#x2032;,4&#x2032;-non-bridged nucleic acid residue(s) is(are) present between the above-mentioned both terminals, and one or more bases in the nucleic acid residue(s) of the above-mentioned 2&#x2032;,4&#x2032;-non-bridged nucleic acid residue(s) is/are modified.

A compound represented by formula I or II below or a salt thereof: 

Oligonucleotide and artificial nucleoside having guanidine bridge

Disclosed are bridged nucleosides and nucleotides. The nucleosides of the present invention have a 2',4&#x2032;-bridged structure and are represented by formula I below: An oligonucleotide containing a 2&#x2032;,4&#x2032;-bridged artificial nucleotide of the present invention has a binding affinity for single-stranded RNA comparable to that of known 2&#x2032;,4&#x2032;-BNA/LNA and higher nuclease resistance than LNA. In particular, since the oligonucleotide has a much higher binding affinity for single-stranded RNA than S-oligo, it is expected that the oligonucleotide is applicable to nucleic acid drugs.

Growing community of inventors

Osaka, Japan

Reiko Waki