Abstract: 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-Lx1 . . . (I) and Lx2-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.

Abstract: 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-Lx1 (I) and Lx2-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.

Abstract: The present invention aims to provide a new nucleic acid molecule for suppressing expression of the target gene, which (1) has a gene expression suppressing activity equivalent to or higher than that of siRNA, (2) shows no off-target effect of the sense strand, and (3) makes it possible to design a wider range of antisense strand sequences (extends the range of targetable sequences). Since the nucleic acid molecule of the following formula: wherein each symbol is as defined in the DESCRIPTION, has the superior properties of the above-mentioned (1) to (3), it is extremely useful as a novel gene expression inhibitor that replaces conventional siRNA.

Abstract: The present invention aims to provide a method of producing, more efficiently at a high purity, a phosphoramidite preferable for the production (synthesis) of a nucleic acid. Using a coupling reaction of an ether represented by the following chemical formula (105), an enantiomer, tautomer or stereoisomer thereof, or a salt thereof, and a glycoside compound, phosphoramidite that enables efficient synthesis of nucleic acid can be obtained: wherein n is a positive integer, and R and R? are the same or different and each is a hydrogen atom or a hydroxyl-protecting group.

Abstract: 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?-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?-terminal and/or the 3?-terminal of sgRNA. Stability in vivo can be improved by introducing one or more amino acid derivative linkers into the sgRNA.

Abstract: 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-Lx1 (I) and Lx2-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.

Abstract: 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?-terminus, and said linker region (Lx).

Abstract: The invention provides a single-stranded nucleic acid molecule and a production method thereof. The single-stranded nucleic acid molecule is represented by formula (I): wherein each symbol is as described in the description.

Abstract: The present invention provides a natural type miRNA, which is a single-stranded nucleic acid containing X region and Y region, wherein the 3?-terminus of said X region and the 5?-terminus of said Y region are linked via a linker region of a non-nucleotide structure, the X region contains (a) a guide strand sequence or (b) a passenger strand sequence of a mature miRNA, when the X region contains (a), the Y region contains a passenger strand sequence of the mature miRNA, when the X region contains (b), the Y region contains a guide strand sequence of the mature miRNA, and the guide strand sequence and the passenger strand sequence form a double-stranded structure.

Abstract: 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?-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.

Abstract: The present invention aims to provide a nucleic acid molecule having improved stability in serum and capable of exhibiting a gene expression regulation function after transfer into the cell. A cyclic nucleic acid molecule represented by the following formula (A): wherein each symbol is as described in the DESCRIPTION can be synthesized easily at a low cost, and can inhibit the translation of a protein encoded by the gene. Since the cyclic nucleic acid molecule of the present invention can inhibit the expression of a target gene as described above, for example, it is useful as a pharmaceutical product, a diagnostic agent, an agricultural chemical, and a tool for conducting research on agriculture, medical science, life science, and the like.

Abstract: 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?-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?-terminal and/or the 3?-terminal of sgRNA. Stability in vivo can be improved by introducing one or more amino acid derivative linkers into the sgRNA.

Abstract: 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.

Abstract: 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?-side, a 5?-side region (Xc), a linker region (Lx), an inner region (Z), a linker region (Ly) and a 3?-side region (Yc) in this order, wherein the inner region (Z) is constituted by linkage of the inner 5?-side region (X) and the inner 3?-side region (Y), the 5?-side region (Xc) is complementary to the inner 5?-side region (X), the 3?-side region (Yc) is complementary to the inner 3?-side region (Y), at least one of the inner region (Z), the 5?-side region (Xc) and the 3?-side region (Yc) comprises an expression inhibitory sequence that inhibits expression of a target gene, and at least one of the 5?-terminus, the 3?-terminus, the linker region (Lx) and the linker region (Ly) is bound to a bio-related substance.

Abstract: 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.

Abstract: The present invention provides a natural type miRNA, which is a single-stranded nucleic acid containing X region and Y region, wherein the 3?-terminus of said X region and the 5?-terminus of said Y region are linked via a linker region of a non-nucleotide structure, the X region contains (a) a guide strand sequence or (b) a passenger strand sequence of a mature miRNA, when the X region contains (a), the Y region contains a passenger strand sequence of the mature miRNA, when the X region contains (b), the Y region contains a guide strand sequence of the mature miRNA, and the guide strand sequence and the passenger strand sequence form a double-stranded structure.

Abstract: 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?-terminus, and said linker region (Lx).

Abstract: 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.

Abstract: 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?-side, a 5?-side region (Xc), a linker region (Lx), an inner region (Z), a linker region (Ly) and a 3?-side region (Yc) in this order, wherein the inner region (Z) is constituted by linkage of the inner 5?-side region (X) and the inner 3?-side region (Y), the 5?-side region (Xc) is complementary to the inner 5?-side region (X), the 3?-side region (Yc) is complementary to the inner 3?-side region (Y), at least one of the inner region (Z), the 5?-side region (Xc) and the 3?-side region (Yc) comprises an expression inhibitory sequence that inhibits expression of a target gene, and at least one of the 5?-terminus, the 3?-terminus, the linker region (Lx) and the linker region (Ly) is bound to a bio-related substance.

Abstract: 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?-side, a 5?-side region (Xc), a linker region (Lx), an inner region (Z), a linker region (Ly) and a 3?-side region (Yc) in this order, wherein the inner region (Z) is constituted by linkage of the inner 5?-side region (X) and the inner 3?-side region (Y), the 5?-side region (Xc) is complementary to the inner 5?-side region (X), the 3?-side region (Yc) is complementary to the inner 3?-side region (Y), at least one of the inner region (Z), the 5?-side region (Xc) and the 3?-side region (Yc) comprises an expression inhibitory sequence that inhibits expression of a target gene, and at least one of the 5?-terminus, the 3?-terminus, the linker region (Lx) and the linker region (Ly) is bound to a bio-related substance.