Title:
STABILIZATION OF DOUBLE-STRANDED RNA BY CATIONIC ARTIFICIAL OLIGOSACCHARIDE
Document Type and Number:
WIPO Patent Application WO/2020/090211
Kind Code:
A1
Abstract:
Provided is a method of adjusting the stability of double-stranded RNA, the method comprising (1) a step of introducing a modification into the backbone of double-stranded RNA; and (2) a step of bringing the double-stranded RNA provided by step (1) into contact with a cationic oligosaccharide, e.g., 2,6-diamino-2,6-dideoxy-β-(1→4)-D-galactopyranose tetramer. Also provided is a nucleic acid composition comprising a complex between backbone-modified double-stranded RNA and a cationic oligosaccharide, e.g., 2,6-diamino-2,6-dideoxy-β-(1→4)-D-galactopyranose tetramer, wherein the nucleic acid composition has a pharmaceutical activity equivalent to unmodified double-stranded RNA and has a serum half-life that is at least five times longer than that of the unmodified double-stranded RNA.
Inventors:
SHIBASAKI FUTOSHI (JP)
IRIE ATSUSHI (JP)
WADA TAKESHI (JP)
HARA RINTARO (JP)
SATO KAZUKI (JP)
IRIE ATSUSHI (JP)
WADA TAKESHI (JP)
HARA RINTARO (JP)
SATO KAZUKI (JP)
Application Number:
PCT/JP2019/034105
Publication Date:
May 07, 2020
Filing Date:
August 30, 2019
Export Citation:
Assignee:
TOKYO METROPOLITAN INST MEDICAL SCIENCE (JP)
UNIV OF SCIENCE TOKYO (JP)
UNIV OF SCIENCE TOKYO (JP)
International Classes:
C12N15/11; A61K31/7088; A61K48/00; C07H5/06; C07H21/02; C12N15/113
Other References:
HARA, IWATA: "Novel molecular technology to achieve stabilization and high activation of nucleic acid medicines", DEMENTIA JAPAN, vol. 32, no. 4, 15 October 2018 (2018-10-15), pages 597 - 606
HARA IWATA RINTARO ET AL.: "Double-stranded RNA-binding artificial cationic oligosaccharides stabilizing siRNAs with a low N/P ratio", ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 15, 2017, pages 1710 - 1717, XP055705545
HARA IWATA RINTARO ET AL.: "Artificial cationic oligosaccharides for heteroduplex oligonucleotide-type drugs", SCIENTIFIC REPORTS, vol. 8, 12 March 2018 (2018-03-12), XP055705557, DOI: 10.1038/s41598-018-22161-8
IRIE, ATSUSHI ET AL.: "Stabilizing siRNA by Combining Cationic Artificial Oligosaccharides and Modified Nucleic Acids.", ABSTRACTS OF THE 139TH ANNUAL MEETING OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 5 March 2019 (2019-03-05), pages 191
HARA IWATA RINTARO ET AL.: "Double-stranded RNA-binding artificial cationic oligosaccharides stabilizing siRNAs with a low N/P ratio", ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 15, 2017, pages 1710 - 1717, XP055705545
HARA IWATA RINTARO ET AL.: "Artificial cationic oligosaccharides for heteroduplex oligonucleotide-type drugs", SCIENTIFIC REPORTS, vol. 8, 12 March 2018 (2018-03-12), XP055705557, DOI: 10.1038/s41598-018-22161-8
IRIE, ATSUSHI ET AL.: "Stabilizing siRNA by Combining Cationic Artificial Oligosaccharides and Modified Nucleic Acids.", ABSTRACTS OF THE 139TH ANNUAL MEETING OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 5 March 2019 (2019-03-05), pages 191
Attorney, Agent or Firm:
OKUYAMA, Shoichi et al. (JP)
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