OLIGONUCLEOTIDE MODULATORS OF THE TOLL-LIKE RECEPTOR PATHWAY

• Main Authors: ELENA FEINSTEIN, SHARON AVKIN-NACHUM, HAGAR KALINSKI, SVETLANA ADAMSKY, IGOR METT
• Format: Patent
• Language: English; Japanese
• Published: 31.08.2017
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

PROBLEM TO BE SOLVED: To provide a dsRNA compound that down-regulates the expression of a Toll-like receptor gene useful for treatment of acute or chronic inflammation, etc.SOLUTION: Provided is a double stranded nucleic acid molecule comprising a sense strand and an antisense strand and having the following structure: 5'N1-(N)x-Z3' (antisense strand), 3'Z'-N2-(N')y-z"5' (sense strand). Here, each N2, N, and N' is a ribonucleotide that may be unmodified or modified, or an unconventional moiety; (N)x is complementary to a TLR4 mRNA sequence; the sequence of (N')y is complementary to a (N)x sequence; x and y are integers from 17 to 24; N1 is an unmodified or modified ribonucleotide covalently bonded to (N)x and mismatched to the target RNA; z" is present or absent, if present a capping moiety; Z and Z' are present or absent, if present, from 1 to 5 consecutive nucleotides covalently linked at the 3' end of the existing strand, a contiguous non-nucleotide part, or a combination thereof.SELECTED DRAWING: None 【課題】急性又は慢性の炎症等の治療に有用なＴｏｌｌ様受容体遺伝子の発現を下方調節するｄｓＲＮＡ化合物の提供。【解決手段】以下の構造を有するセンス鎖及びアンチセンス鎖を含む二本鎖核酸分子。５'Ｎ１−（Ｎ）ｘ−Ｚ３'（アンチセンス鎖）、３'Ｚ'−Ｎ２−（Ｎ'）ｙ−ｚ"５'（センス鎖）。（各Ｎ２、Ｎ及びＮ'は未修飾或いは修飾されたリボヌクレオチド又は非定型；（Ｎ）ｘはＴＬＲ４ｍＲＮＡ配列に相補的；（Ｎ'）ｙの配列は（Ｎ）ｘの配列に相補的；ｘ及びｙは１７〜２４の整数；Ｎ１は（Ｎ）ｘに共有結合し標的ＲＮＡに対してミスマッチである未修飾或いは修飾されたリボヌクレオチド；ｚ"は存在又は非存在であって、存在するならばキャッピング部分；Ｚ及びＺ'は存在又は非存在で、存在するならば、存在する鎖の３'末端にて共有結合する１〜５の連続するヌクレオチド、連続する非ヌクレオチド部分又はその組み合わせ）【選択図】なし