Bonac Corporation

Nippon Shinyaku Company, Ltd.

Toray Industries, Inc.

Tokyo Medical University

Yano, Junichi

Ohgi, Tadaaki

Tadaaki Ohgi

Tomohiro Hamasaki

Eriko Aoki

Hiroshi Suzuki

Hisao Shirohzu

Akihiro Itoh

Kouichi Ishiyama

Hirotake Hayashi

Shiori Kato

Junichi Yano

Junzo Seki

Yoshihisa Shibata

Kenji Sempuku

Toshihiro Ueda

Takashi Kinoshita

Chisato Emura

Shinji Matsuyama

Yano Junichi

Yasuhiko Yoshida

Takayuki Mizutani

Masahiko Kuroda

Katsuhiko Iseki

Tatsuya Oyama

Keiichi Okimura

Hideaki Inada

Kazuko Hirabayashi

Satoru Sonoke

Tomohiro Terada

Munetaka Kunishima

Shinichiro Ohno

Tatsuya Fujita

Hiroto Yoshifusa

Kyohei Koshimoto

Yutaka Masutomi

Koichi Ishiyama

Kazuhisa Kandori

Yutaka Room 2-1C Nippon Shinyaku Masutomi

A method produces a hairpin single-stranded RNA molecule capable of inhibiting expression of a target gene, including the step of reacting a first single-stranded oligo-RNA molecule represented by formula (I) with a second single-stranded oligo-RNA molecule represented by formula (II) in a mixed solvent including a buffer solution and a hydrophilic organic solvent in the presence of a dehydration condensation agent: 5′-Xc-Lx(I) and Lx-X—Y-Ly-Yc-3′ (II), wherein the dehydration condensation agent is selected from the group consisting of a triazine-based dehydration condensation agent, a uronium-based dehydration condensation agent including an N-hydroxy nitrogen-containing aromatic ring structure, a carbodiimide-based dehydration condensation agent, a 2-halopyridinium-based dehydration condensation agent, and a formamidinium-based dehydration condensation agent.

Method of producing hairpin single-stranded RNA molecules

The invention provides an artificial sgRNA and a CRISPR/Cas9 system by combining the artificial sgRNA and Cas9. Activity of the sgRNA can be retained even when a nucleotide linker region for forming a single strand by linking the 3'-terminal of crRNA and the 5&#x2032;-terminal of tracrRNA in sgRNA is substituted with an amino acid derivative linker, when the linker region existing between stem-loop 1 and stem-loop 2 of tracrRNA and/or the loop portion of stem-loop 2 are/is substituted with an amino acid derivative linker, or when an amino acid derivative linker is added/inserted into the vicinity of the 5&#x2032;-terminal and/or the 3&#x2032;-terminal of sgRNA. Stability in vivo can be improved by introducing one or more amino acid derivative linkers into the sgRNA.

Artificial single guide RNA and use thereof

The present invention provides a single-stranded nucleic acid molecule having a delivery function and capable of inhibiting expression of a target gene. The single-stranded nucleic acid molecule of the present invention is a single-stranded nucleic acid molecule composed of a region (Xc), a linker region (Lx) and a region (X), wherein said region (Xc) is complementary to said region (X), at least one of said region (X) and said region (Xc) contains an expression inhibitory sequence that inhibits expression of the target gene, and a bio-related substance having a delivery function is bonded to at least one selected from the group consisting of the 5'-terminus, the 3&#x2032;-terminus, and said linker region (Lx).

Single-stranded nucleic acid molecule having delivery function and gene expression regulating ability

The present invention provides a natural type miRNA,

Natural type miRNA for controlling gene expression, and use of same

The invention provides an artificial match-type miRNA utilizing miRNA. In particular, the invention provides a single strand nucleic acid containing an X region and a Y region, wherein the 3'-terminal of the X region and the 5&#x2032;-terminal of the Y region are linked via a linker region of a non-nucleotide structure, the X region contains a guide strand sequence of a mature miRNA, and the Y region contains a sequence completely complementary to the X region is an artificial match-type miRNA. The artificial match-type miRNA can suppress expression of the target gene.

Artificial match-type miRNA for controlling gene expression and use therefor

The invention provides a production method of a glycoside compound or a salt thereof, which includes subjecting a thioether compound and an alcohol compound to a coupling reaction in the presence of a halogenating agent, a desiccant and a Lewis acid, and then distillation in the presence of at least one kind of additive selected from a sulfur-containing antioxidant and a maleimide group-containing compound to give a thioether compound and a step of subjecting a glycoside compound and a thioether compound to a coupling reaction in the presence of a halogenating agent, a desiccant and a Lewis acid to give a glycoside compound. By this method, a phosphoramidite preferable for the production (synthesis) of a nucleic acid can be produced more efficiently at a high purity.

Method for producing glycoside compounds

The invention provides a single-stranded nucleic acid capable of inhibiting expression of a target gene having a delivery function. The nucleic acid contains, from the 5'-side to the 3&#x2032;-side, a 5&#x2032;-side region (Xc), a linker region (Lx), an inner region (Z), a linker region (Ly) and a 3&#x2032;-side region (Yc) in this order, wherein the inner region (Z) is constituted by linkage of the inner 5&#x2032;-side region (X) and the inner 3&#x2032;-side region (Y), the 5&#x2032;-side region (Xc) is complementary to the inner 5&#x2032;-side region (X), the 3&#x2032;-side region (Yc) is complementary to the inner 3&#x2032;-side region (Y), at least one of the inner region (Z), the 5&#x2032;-side region (Xc) and the 3&#x2032;-side region (Yc) comprises an expression inhibitory sequence that inhibits expression of a target gene, and at least one of the 5&#x2032;-terminus, the 3&#x2032;-terminus, the linker region (Lx) and the linker region (Ly) is bound to a bio-related substance.

Single-stranded nucleic acid molecule for regulating expression of gene having delivering function

The invention provides a microRNA inhibitor that has two or more sequences complementary to the sequence of microRNA to be the target of inhibition, which two or more complementary sequences are linked via one or more linker residues.

Micro-RNA inhibitor

The invention provides a single-stranded nucleic acid molecule containing an expression inhibitory sequence that inhibits expression of a target gene, region (X), linker region (Lx), and region (Xc), wherein the linker region (Lx) is linked between the region (Xc) and the region (Xc), the region (Xc) is complementary to the region (X), at least one of the region (X) and the region (Xc) contains the expression inhibitory sequence, and the linker region (Lx) contains an atomic group derived from an amino acid. The single-stranded nucleic acid molecule can inhibit expression of the target gene.

Single-stranded nucleic acid molecule having amino acid backbone

Micro-RMA inhibitor

The present invention provides a process for preparing an isotope-containing phosphate compound easily. The process for preparing an isotope-containing phosphate compound according to the present invention includes the step of: oxidizing a trivalent phosphorus compound with an oxidizing agent containing an isotope to synthesize a pentavalent phosphate compound to which the isotope has been introduced. The present invention preferably is applied to the synthesis of nucleic acids such as DNA and RNA, for example. The isotope preferably is a stable isotope. The oxidizing agent preferably is HO, 3H-1,2-benzodithiol 3-one 1,1-dioxide havingS, or a diisopropylethylamine-borane complex havingB, for example.

Process for preparing phosphate compound bearing isotope

Provided is a novel nucleic acid molecule that can be produced easily and efficiently and can inhibit the expression of a gene. The nucleic acid molecule is a single-stranded nucleic acid molecule including an expression inhibitory sequence that inhibits expression of a target gene. The single-stranded nucleic acid molecule includes: a region (X); a linker region (Lx); and a region (Xc). The linker region (Lx) is linked between the regions (Xc) and (Xc). The region (Xc) is complementary to the region (X). At least one of the regions (X) and (Xc) includes the expression inhibitory sequence. The linker region (Lx) has a non-nucleotide structure including at least one of a pyrrolidine skeleton and a piperidine skeleton. According to this single-stranded nucleic acid molecule, it is possible to inhibit the expression of the target gene.

Single-stranded nucleic acid molecule having nitrogen-containing alicyclic skeleton

Provided is a novel nucleic acid molecule that is a single-stranded nucleic acid molecule including an expression inhibitory sequence that inhibits expression of a target gene. The single-stranded nucleic acid molecule includes, in sequence from the 5' side to the 3&#x2032; side: a 5&#x2032; side region (Xc); an inner region (Z); and a 3&#x2032; side region (Yc). The inner region (Z) is composed of an inner 5&#x2032; side region (X) and an inner 3&#x2032; side region (Y) that are linked to each other. The 5&#x2032; side region (Xc) is complementary to the inner 5&#x2032; side region (X). The 3&#x2032; side region (Yc) is complementary to the inner 3&#x2032; side region (Y). At least one of the inner region (Z), the 5&#x2032; side region (Xc), and the 3&#x2032; side region (Yc) includes the expression inhibitory sequence.

Single-stranded nucleic acid molecule for controlling gene expression

Growing community of inventors

Kurume, Japan

Tadaaki Ohgi