8- RNA 8- RNA NUCLEIC ACIDS INDUCING RNA INTERFERENCE INCLUDING 8-OXOGUANINE MICRO RNA INCLUDING 8-OXOGUANINE AND USE THEREOF

• Main Authors: SEOK HEE YOUNG, CHI SUNG WOOK
• Format: Patent
• Language: English; Korean
• Published: 07.06.2021
• Subjects: AGRICULTURE; ANIMAL HUSBANDRY; BEER; BIOCHEMISTRY; CARE OF BIRDS, FISHES, INSECTS; CHEMISTRY; COMPOSITIONS OR TEST PAPERS THEREFOR; COMPOSITIONS THEREOF; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES; CULTURE MEDIA; ENZYMOLOGY; FISHING; FORESTRY; HUMAN NECESSITIES; HUNTING; HYGIENE; MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; NEW BREEDS OF ANIMALS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROCESSES OF PREPARING SUCH COMPOSITIONS; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; TRAPPING; VINEGAR; WINE

In the present invention, it has been confirmed that, when an RNA interference-inducing nucleic acid in which the 1st to 9th nucleotides from the 5'-end of one or more single strands of a double-stranded nucleic acid comprise at least one 8-oxoguanine (o^8G), and a modified nucleic acid which specifically binds to microRNA and in which one or more guanines (G) from among the 1st to 9th nucleotides from the 5'-end are modified to 8-oxoguanine (o^8G) are produced and administered to cells or mice, various pathophysiological phenomena are induced. In addition, the positions where G > T modifications occur have been identified in cDNA produced through the reverse transcription of microRNA in which guanine (G) is oxidatively modified to 8-oxoguanine (o^8G) by oxidative stress in a seed region of microRNA, to confirm the positions where oxidative modification to 8-oxoguanine has occurred. 본 발명에서는 핵산의 이중 가닥 중 하나 이상의 단일 가닥에서, 5' 말단으로부터 1번째 내지 9번째 뉴클레오타이드는 하나 이상의 8-옥소구아닌(8-oxoguanine; o8G)을 포함하는 RNA 간섭 유도 핵산 및 5'말단으로부터 1번째 내지 9번째 뉴클레오타이드 중 하나 이상의 구아닌 (G)이 8-옥소구아닌(o8G)으로 변형된 마이크로RNA와 특이적으로 결합하는 변형 핵산을 제조하여 세포 또는 마우스에 투여하였을 때 다양한 병리생리학적 현상이 유도되는 것을 확인하였다. 또한, 산화 스트레스로 인해 마이크로RNA의 발단지역 (seed region)에서 구아닌(G)이 8-옥소구아닌(o8G)으로 산화 변형이 일어난 마이크로RNA의 역전사를 통해 제조된 cDNA에서 G>T로 변형이 일어난 위치를 동정하여, 8-옥소구아닌으로 산화 변형이 일어난 위치를 확인하였다.