Tokyo Medical and Dental University

Kumiai Chemical Industry Co., Ltd.

Osaka University

Kotaro Yoshioka

Takanori Yokota

Kazutaka Nishina

Kentaro Kawazoe

Tetsuya Nagata

Satoshi Obika

Hidehiro Mizusawa

Takenori Shimo

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.

Nucleic acid with reduced toxicity

Provided is a nucleic acid strand that can efficiently deliver an antisense oligonucleotide into the body, particularly a nucleic acid complex comprising a first nucleic acid strand and a second nucleic acid strand, wherein the first nucleic acid strand includes a base sequence that is capable of hybridizing with at least a portion of a target transcription product, and exerts an antisense effect on the target transcription product; the second nucleic acid strand includes a complementary region having a base sequence complementary to the first nucleic acid strand and at least one overhang region located on the 5' and/or 3&#x2032; side of the complementary region; and the first nucleic acid strand is annealed to the complementary region in the second nucleic acid strand.

Double-stranded nucleic acid complex having overhang

Disclosed are double-stranded nucleic acid agents that can deliver a therapeutic oligonucleotide within a biological sample, and methods for using the same. In one embodiment, the double-stranded nucleic acid agent comprises a first strand comprising a first RNA region, and a second strand comprising a first DNA region, wherein said first RNA region and said first DNA region are hybridized as a RNA/DNA heteroduplex. Said first strand further comprises a nucleic acid therapeutic oligonucleotide region that is capable of being cleaved from at least one nucleotide in said first RNA region. Methods for using the double-stranded nucleic acid agents include methods for delivering the therapeutic oligonucleotide as a single strand by cleaving it from at least a portion of the first RNA region. The methods further include delivering the double-stranded nucleic acid agent and thus the therapeutic oligonucleotide to a target site within the body of a treatment subject.

Double-stranded agents for delivering therapeutic oligonucleotides

Problem to be Solved It is intended to provide an industrially preferable fluoroalkylating agent and use thereof. Solution The present invention provides a fluoroalkylating agent represented by the general formula (1) wherein Ris a C1 to C8 fluoroalkyl group; Rand Rare each independently a C1 to C12 alkyl group or the like; Yto Yare each independently a hydrogen atom, a halogen atom, or the like; and Xis a monovalent anion.  A compound of the general formula (3): R&#x2014;S&#x2014;Rhaving an introduced C1 to C8 fluoroalkyl group is easily obtained by reacting a compound of the general formula (2): R&#x2014;S&#x2014;Z wherein Ris a hydrocarbon group or the like; and Z is a leaving group, with the compound of the general formula (1).

Fluoroalkylating agent

Disclosed are double-stranded antisense nucleic acid complexes that can efficiently alter the processing of RNA in a cell via an antisense effect, and methods for using the same. One method comprises contacting with the cell a double-stranded nucleic acid complex comprising: a first nucleic acid strand annealed to a second nucleic acid strand, wherein: the first nucleic acid strand comprises (i) nucleotides independently selected from natural DNA nucleotides, modified DNA nucleotides, and nucleotide analogs, (ii) no regions that have 4 or more consecutive natural DNA nucleotides, (iii) the total number of natural DNA nucleotides, modified DNA nucleotides, and nucleotide analogs in the first nucleic acid strand is from 8 to 100, and (iv) the first nucleic acid strand is capable of hybridizing to RNA inside of the cell; and the second nucleic acid strand comprises nucleotides independently selected from natural RNA nucleotides, modified RNA nucleotides, and nucleotide analogs.

Growing community of inventors

Tokyo, Japan

Kotaro Yoshioka