Osaka University

Tokyo Medical and Dental University

National Institutes of Biomedical Innovation, Health and Nutrition

Other

Takeshi Imanishi

Mitsubishi Tanabe Pharma Corporation

National Cerebral and Cardiovascular Center

Riken Corporation

Sankyo Company, Limited

Kobe University

Aichi Medical University

Tokyo University of Science Education Foundation Administrative Organization

Luxna Biotech Co., Ltd.

Tokyo University of Science Educational Foundation Administrative Organization

Imanishi, Takeshi

Satoshi Obika

Takanori Yokota

Kazutaka Nishina

Yuya Kasahara

Hidehiro Mizusawa

Reiko Waki

Kosuke Ito

Masahiko Horiba

Takao Inoue

Tokuyuki Yoshida

Takaki Habuchi

Takao Yamaguchi

Tsuyoshi Yamamoto

Hiroaki Sawamoto

Shinji Kumagai

Kunihiko Morihiro

Atsushi Mikami

Hiroyuki Furukawa

Atsushi Yamashita

Masaaki Suzuki

Yasuyoshi Watanabe

Takao Suzuki

Eiji Kawanishi

Hideki Mochizuki

Tetsuji Yamaoka

Hisashi Doi

Kotaro Yoshioka

Tetsuya Kodama

Masayuki Nakamori

Sachiro Kakinoki

Mariko Shiba

Tadayuki Kobayashi

Shuhei Yamakoshi

Takenori Shimo

Keisuke Narukawa

Hidetaka Torigoe

Tetuya Nagata

Yoichi Tachibana

Motoki Sawamura

Kiyomi Sasaki

Takeshi Kuboyama

Yoshiyuki Hari

Mariko Harada-Shiba

Aiko Yahara

Masaru Nishida

Kazuyuki Miyashita

Yuuki Aral

Kosei Takeuchi

Masahito Shimojo

Masaki Yamagami

Fumito Wada

Tadashi Umemoto

Takaya Sugiura

Go Kato

Tomo Araki

Akira Kikuchi

Takumi Fukumoto

Shinji Matsumoto

Yutaro Kotobuki

Masayuki Utsugi

Keisuke Tachibana

Tachibana Yoichi

Yuuki Arai

Disclosed are a 5′-modified nucleoside and a nucleotide using the same. The nucleoside of the present invention is represented by the formula (I) below. The 5′-modified nucleoside of the present invention is usable as a substitute for a phosphorothioate-modified nucleic acid, which has a risk of, for example, accumulation in a specific organ. The 5′-modified nucleoside also has excellent industrial productivity because a diastereomer separation step is not involved in the production process thereof.

5'-modified nucleoside and nucleotide using same

A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5' terminal side of the region, (c) one or more nucleotide analogs located on 3′ terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides.

Chimeric double-stranded nucleic acid

The present invention provides a novel bridged artificial nucleic acid and an oligomer containing the same as a monomer. The present invention provides specifically a compound represented by general formula (I) (wherein each symbol is the same as defined in the specification) or salts thereof; as well as an oligonucleotide compound represented by general formula (I′) (wherein each symbol is the same as defined in the specification) or salts thereof.

Crosslinked artificial nucleic acid ALNA

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 purpose of the present invention is to provide an antisense oligonucleotide that targets an ARL4C molecule and exerts an antitumor effect in vivo, and a nucleic acid drug using the antisense oligonucleotide. An antisense oligonucleotide that has a base sequence consisting of at least 10 consecutive bases contained in the base sequence represented by SEQ ID NO: 1. This antisense oligonucleotide targets an ARL4C molecule and thus can inhibit the expression of ARL4C in a tumor cell in vitro and suppress the migration and proliferation thereof. When systemically administered, moreover, the antisense oligonucleotide can exert an excellent antitumor effect in vivo too.

Antisense oligonucleotide targeting ARL4C molecule, and nucleic acid drug using antisense oligonucleotide

The present invention aims to provide a nucleic acid compound that hardly forms non-Watson-Crick base pairs, and an oligonucleotide containing the nucleic acid compound and showing reduced non-specific binding with nucleic acids other than the target nucleic acid. The nucleic acid compound according to the present invention is characterized in that the 2-position carbonyl group of the pyrimidine base is functionally converted (Xand Xare each independently S or Se), and that the 2′-position and the 4′-position are bridged in a particular structure. The oligonucleotide according to the present invention is characterized in that at least one of thymidine and uridine is the nucleic acid compound.

Nucleic acid compound and oligonucleotide

Disclosed is an oligonucleotide or a pharmacologically acceptable salt thereof, wherein the oligonucleotide comprises at least one defined nucleoside structure, can bind to a human nSR100 gene and has human nSR100 expression inhibiting activity. The oligonucleotide has a length of 12 to 20 mer, and is complementary to a defined target region. Further, disclosed is an nSR100 gene expression inhibitor and a cancer therapeutic agent containing the oligonucleotide or the pharmacologically acceptable salt thereof. The cancer therapeutic agent is used for treatment of small cell lung cancer, prostate cancer, or breast cancer.

Small cell lung cancer therapeutic agent containing oligonucleotide

The present invention provides an antisense oligonucleotide for inhibiting biosynthesis of chondroitin sulfate. The antisense oligonucleotide comprises at least one modified nucleotide, wherein the antisense oligonucleotide suppresses expression of one or both of the chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT1) gene and the chondroitin sulfate N-acetylgalactosaminyltransferase-2 (CSGalNAcT2) gene.

Antisense nucleic acid for inhibiting biosynthesis of chondroitin sulfate

The present invention aims to provide a nucleic acid compound that hardly forms non-Watson-Crick base pairs, and an oligonucleotide containing the nucleic acid compound and showing reduced non-specific binding with nucleic acids other than the target nucleic acid. The nucleic acid compound according to the present invention is characterized in that the 2-position carbonyl group of the pyrimidine base is functionally converted (Xand Xare each independently S or Se), and that the 2'-position and the 4&#x2032;-position are bridged in a particular structure. The oligonucleotide according to the present invention is characterized in that at least one of thymidine and uridine is the nucleic acid compound.

Provided is an oligonucleotide conjugate comprising an oligonucleotide and two or more linearly connected asialoglycoprotein receptor-binding molecules attached to the oligonucleotide, wherein the oligonucleotide comprises a locked nucleoside analog having a bridging structure between the 4' and 2&#x2032; positions, is complementary to a human PCSK9 gene, and has inhibitory activity on the expression of the human PCSK9 gene. The oligonucleotide conjugate of the present invention can be used in the field of pharmaceutical products, in particular, the field of the development and production of therapeutic agents for diseases associated with a high LDL cholesterol level.

Antisense nucleic acid targeting PCSK9

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.

The present invention can provide a nucleic acid medicine which has a higher effect and a more prolonged effect of inhibiting the expression of &#x3b1;-synudein can be provided. Disclosed is the oligonucleotide or a pharmacologically acceptable salt thereof, the oligonucleotide containing at least one nucleoside structure represented by Formula (I): (where each of Base and A are defined substituent or structure), can bind to an &#x3b1;-synudein gene, has activity for inhibiting expression of the &#x3b1;-synudein gene, and is complementary to the &#x3b1;-synudein gene, and the oligonucleotide has a length of twelve to twenty bases. 

&#x3b1;-synuclein expression inhibitor

A method of reducing the level of a transcription product in a cell comprising contacting with the cell a composition comprising a double-stranded nucleic acid complex comprising a first nucleic acid strand annealed to a second nucleic acid strand, wherein: (i) the first nucleic acid strand hybridizes to the transcription product and comprises (a) a region consisting of at least 4 consecutive nucleotides that are recognized by RNase H when the strand is hybridized to the transcription product, (b) one or more nucleotide analogs located on 5' terminal side of the region, (c) one or more nucleotide analogs located on 3&#x2032; terminal side of the region and (d) a total number of nucleotides and nucleotide analogs ranging from 8 to 35 nucleotides and (ii) the second nucleic acid strand comprises (a) nucleotides and optionally nucleotide analogs and (b) at least 4 consecutive RNA nucleotides.

A method for preparing a compound represented by general formula I: or a salt thereof includes a step of reacting a compound represented by formula II: with a reducing agent to cleave an oxazolidine ring fused to a cycle A'. The reducing agent includes at least one of phosphines, metal hydrides, or transition metal catalysts in the presence of hydrogen gas.

Bridged nucleic acid GuNA, method for producing same, and intermediate compound

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

Oligonucleotide and artificial nucleoside having guanidine bridge

Growing community of inventors

Osaka, Japan

Satoshi Obika