Abstract: The present disclosure provides a method for producing a nucleic acid molecule. Specifically, the present disclosure achieves process shortening and a dramatic improvement in ligation efficiency by using nucleic acid splints. That is, the present disclosure provides a method for producing a polynucleotide molecule having a specific sequence, the method including: 1) providing two or more polynucleotide fragment molecules including a portion of the specific sequence; and 2) ligating the two or more polynucleotide fragment molecules in the presence of two or more nucleic acid splints, wherein each sequence of the two or more polynucleotide fragment molecules when assembled constitutes the specific sequence, the nucleic acid splints are substantially complementary to the polynucleotide molecule, and at least two of the nucleic acid splints include a sequence which is substantially free of deletions when aligned with the specific sequence.

Abstract: Provided is a novel technique for treating cancer using structurally-reinforced S-TuD. Provided are: a composition for the prevention or treatment of tumors, said composition comprising an miRNA inhibitory complex including RNA of analog thereof; and a method for preventing or treating tumors using said composition. The miRNA inhibitory complex preferably includes at least one double-stranded structure and an miRNA-binding sequence. Two strands of the miRNA binding sequence preferably bind individually to two strands on at least one end of the double-stranded structure. According to some of the aspects of the present invention, there is provided a delivery system for delivering such an miRNA inhibitory complex.

Abstract: Disclosed is a double-stranded oligonucleotide decoy including two transcription factor-binding sites, while keeping its size small. The double-stranded oligonucleotide decoy showing binding affinities for two transcription factors includes a first binding site for a first transcription factor and a second binding site for a second transcription factor. A first strand including the sense strand of the first binding site and a second strand including the sense strand of the second binding site are hybridized to form a double strand in which the sense strand of the first binding site and the sense strand of the second binding site are at least partly hybridized.

Abstract: Provided are non-aggregating immunostimulatory oligonucleotides. The present invention also provides a delivery agent for an immunostimulatory-oligonucleotide nucleic acid medicine, said delivery agent including a nucleic acid that contains a phosphorothioated nucleotide. According to another aspect, the present invention further provides an oligonucleotide including a bioactive core, and a nucleic acid that contains a phosphorothioated nucleotide. The present invention yet further provides an immunostimulator including the bioactive core of a type A/D, type B/K, or type C immunostimulatory oligonucleotide.

Abstract: The present invention pertains to a method for synthesizing a ribonucleic acid H-phosphonate monomer, and a method for performing oligonucleotide synthesis in which said monomer is used. The present invention pertains to a method for manufacturing an inexpensively manufacturable H-phosphonate nucleoside derivative in which selective protection is provided to position 2? of a ribonucleoside monomer required in RNA oligonucleotide synthesis. The present invention is characterized in that: hydroxyl groups in position 2? and position 3?, which have slightly different reactivity, are caused to react with an aromatic acyl halide at low temperature to selectively esterify position 2?; and subsequently the hydroxyl group at position 3? in one pot is captured by a phosphityl group to prevent position 2? and position 3? transfer of the acyl group.

Abstract: The present invention pertains to the improvement of a miRNA inhibitor (a synthesized Tough Decoy (S-TuD)). The present invention provides a miRNA inhibitory complex including RNA or an analog thereof, wherein the RNA inhibitory complex includes at least one double-stranded structure and a miRNA binding sequence, each of two strands of the miRNA binding sequence being bound to two strands of at least one end of the double-stranded structure, and the miRNA inhibitory complex further includes at least one crosslinked nucleic acid.

Abstract: Disclosed is a double-stranded oligonucleotide decoy including two transcription factor-binding sites, while keeping its size small. The double-stranded oligonucleotide decoy showing binding affinities for two transcription factors includes a first binding site for a first transcription factor and a second binding site for a second transcription factor. A first strand including the sense strand of the first binding site and a second strand including the sense strand of the second binding site are hybridized to form a double strand in which the sense strand of the first binding site and the sense strand of the second binding site are at least partly hybridized.