Abstract: Provided is a drug that allows highly-efficient skipping of exon. The present invention provides an antisense oligomer wherein two or more unit oligomers targeting sequences that are neither consecutive nor overlap with each other in the same exon are connected.

Abstract: A problem to be solved by the present invention is to provide a double-stranded nucleic acid complex having a reduced toxicity whose effectiveness is not impaired. Provided is a double-stranded nucleic acid complex comprising a first nucleic acid strand and a second nucleic acid strand, wherein: said first nucleic acid strand is capable of hybridizing to at least part of a target gene or a transcription product thereof, and has an antisense effect on said target gene or transcription product thereof, said second nucleic acid strand comprises a base sequence complementary to said first nucleic acid strand, and said first nucleic acid strand and/or said second nucleic acid strand comprises at least one bridged non-natural nucleoside represented by formula (I) or formula (II) (wherein R represents a hydrogen atom or a methyl group).

Abstract: In an embodiment, an object of the present invention is to provide a double-stranded nucleic acid complex having a novel structure. In an embodiment, the present invention relates to a nucleic acid complex comprising a first nucleic acid strand and a second nucleic acid strand, wherein said first nucleic acid strand: (1) is capable of hybridizing to at least a part of a target transcriptional product; (2) has an antisense effect on the target transcriptional product; and (3) is a gapmer comprising a central region, and a 5? wing region and a 3? wing region, said second nucleic acid strand comprises at least one sugar-unmodified central region (first exposed region) consisting of one sugar-unmodified ribonucleoside or two or three contiguous sugar-unmodified ribonucleosides linked by an internucleoside bond, which is or are complementary to a part of said first nucleic acid strand, and said first nucleic acid strand is annealed to said second nucleic acid strand.

Abstract: An object of the invention is to provide a low toxicity antisense nucleic acid medicine that can modulate expression of a target transcriptional product in the central nervous system and other sites of a subject. Provided is a low toxicity composition for modulating expression of a target transcriptional product in a site such as the central nervous system of a subject, having a nucleic acid complex formed by annealing together a first nucleic acid strand having an antisense oligonucleotide region with respect to the target transcriptional product, and a second nucleic acid strand having a complementary region that is complementary to at least part of the first nucleic acid strand.

Abstract: Developed and provided is: a nucleic acid agent that is efficiently delivered to the central nervous system, to which drug delivery is inhibited by the blood brain barrier mechanism, and that provides an antisense effect to a target transcription product at the delivery site; and a composition containing such a nucleic acid agent. Provided is a double-stranded nucleic acid complex consisting of a first nucleic acid strand and a second nucleic acid strand that are annealed to each other; wherein the first nucleic acid strand hybridizes with part of a target transcription product and has an antisense effect on the target transcription product; and wherein the second nucleic acid strand includes a base sequence complementary to the first nucleic acid strand and is conjugated to a phosphatidylethanolamine or an analog thereof.

Abstract: A double-stranded nucleic acid complex that can have an excellent activity is provided. In one embodiment, the present invention relates to a double-stranded nucleic acid complex having a first nucleic acid strand and a second nucleic acid strand. The first nucleic acid strand is capable of hybridizing to at least part of a target gene or a transcription thereof, has an antisense effect on the target gene or transcription product thereof, and has at least two morpholino nucleic acids The second nucleic acid strand has a base sequence complementary to the first nucleic acid strand. The first nucleic acid strand is annealed to the second nucleic acid strand.

Abstract: The present invention provides an oligomer which efficiently enables to cause skipping of the 53rd exon in the human dystrophin gene. Also provided is a pharmaceutical composition which causes skipping of the 53rd exon in the human dystrophin gene with a high efficiency.

Abstract: Developed and provided is: a nucleic acid agent that is efficiently delivered to the central nervous system, to which drug delivery is inhibited by the blood brain barrier mechanism, and that provides an antisense effect to a target transcription product at the delivery site; and a composition containing such a nucleic acid agent. Provided is a double-stranded nucleic acid complex consisting of a first nucleic acid strand and a second nucleic acid strand that are annealed to each other; wherein the first nucleic acid strand hybridizes with part of a target transcription product and has an antisense effect on the target transcription product; and wherein the second nucleic acid strand includes a base sequence complementary to the first nucleic acid strand and is conjugated to a phosphatidylethanolamine or an analog thereof.

Abstract: The present invention provides a composition and a method for efficiently delivering a nucleic acid agent to the central nervous system and/or the retina and bringing about antisense effects. Provided is a composition for reducing the expression level of a target transcription product in the central nervous system and/or retina of a subject, the composition including a nucleic acid complex that includes a first nucleic acid strand and a second nucleic acid strand, wherein: the first nucleic acid strand comprises a base sequence capable of hybridizing with at least part of the target transcription product and has an antisense effect on the target transcription product; the second nucleic acid strand comprises a base sequence complementary to the first nucleic acid strand and is conjugated to tocopherol, cholesterol, or an analog thereof; and the first nucleic acid strand is annealed to the second nucleic acid strand.

Abstract: The present invention provides a composition and a method for efficiently delivering a nucleic acid agent to the central nervous system and/or the retina and bringing about antisense effects. Provided is a composition for reducing the expression level of a target transcription product in the central nervous system and/or retina of a subject, the composition including a nucleic acid complex that includes a first nucleic acid strand and a second nucleic acid strand, wherein: the first nucleic acid strand comprises a base sequence capable of hybridizing with at least part of the target transcription product and has an antisense effect on the target transcription product; the second nucleic acid strand comprises a base sequence complementary to the first nucleic acid strand and is conjugated to tocopherol, cholesterol, or an analog thereof; and the first nucleic acid strand is annealed to the second nucleic acid strand.

Abstract: A nucleic acid complex that exhibits an excellent antisense effect in the skeletal muscle and/or heart muscle, and a composition for treating or preventing a muscle disease that develops in the skeletal muscle, heart muscle, and the like having the nucleic acid complex as an active ingredient is disclosed. Also provided is a double-stranded nucleic acid complex in which a first nucleic acid strand that hybridizes to the transcription product of a target gene and has an antisense effect on the transcription product is annealed with a second nucleic acid strand that has a base sequence complementary to the first nucleic acid strand and is bound to cholesterol or analog thereof.

Abstract: Provided is a drug that allows highly-efficient skipping of exon 51 in the human dystrophin gene. The present invention provides an antisense oligomer which enables exon 51 in the human dystrophin gene to be skipped.

Abstract: An object of the present invention is to provide a double-stranded nucleic acid complex having a reduced number of PS modifications in an antisense strand and maintaining an antisense effect. An optimal PS modification pattern for double-stranded nucleic acid complexes is disclosed. Such a nucleic acid complex comprising an antisense strand having an optimal PS modification pattern has a characteristic of having low toxicity and high bioavailability. The double-stranded nucleic acid complex comprising an antisense strand having an optimal PS modification pattern according to the present invention is useful when used as a nucleic acid drug that utilizes inhibition of expression of a specific gene (knockdown), activity that changes the function of coating or non-coding RNA for a specific gene, or activity that changes the function of RNA by inducing exon skipping during processing of pre-mRNA for a specific gene.

Abstract: Provided is a drug that allows highly-efficient skipping of exon. The present invention provides an antisense oligomer wherein two or more unit oligomers targeting sequences that are neither consecutive nor overlap with each other in the same exon are connected.

Abstract: Provided is a drug that allows highly-efficient skipping of exon. The present invention provides an antisense oligomer wherein two or more unit oligomers targeting sequences that are neither consecutive nor overlap with each other in the same exon are connected.

Abstract: The present invention provides an oligomer which efficiently enables to cause skipping of the 53rd exon in the human dystrophin gene. Also provided is a pharmaceutical composition which causes skipping of the 53rd exon in the human dystrophin gene with a high efficiency.

Abstract: The present invention provides an oligomer which efficiently enables to cause skipping of the 53rd exon in the human dystrophin gene. Also provided is a pharmaceutical composition which causes skipping of the 53rd exon in the human dystrophin gene with a high efficiency.

Abstract: The present invention relates to a quantitative amount feed mechanism including a functional unit disposed to be movable along an axis, a drive unit that presses the functional unit with a predetermined driving force to move the functional unit in a first direction along the axis, and an adjustment mechanism that adjusts a movement of the functional unit so that the functional unit moves with the driving force. The adjustment mechanism applies an auxiliary force to the functional unit in a direction the same as the first direction, or applies a reaction force to the functional unit in a second direction opposite to the first direction, in accordance with a difference between a resistance force generated by the movement of the functional unit and the driving force.

Abstract: The present invention relates to a chemical solution pump including a holding member that holds a syringe discharging a chemical solution in association with a movement of a plunger, a drive unit that presses the plunger with a predetermined driving force to move the plunger in a first direction toward an inside of the syringe, and an adjustment mechanism that adjusts the movement of the plunger so that the plunger moves with the driving force. The adjustment mechanism applies an auxiliary force to the plunger in a direction the same as the first direction, or applies a reaction force to the plunger in a second direction opposite to the first direction, in accordance with a difference between a resistance force generated by the movement of the plunger inside the syringe and the driving force.

Abstract: The present invention provides a pharmaceutical agent which causes skipping of the 55th, 45th, 50th or 44th exon in the human dystrophin gene with a high efficiency. The present invention provides an oligomer which efficiently enables to cause skipping of the 55th, 45th, 50th or 44th exon in the human dystrophin gene.