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NUCLEIC ACID DELIVERY ENHANCER

Foreign code F210010470
File No. (S2020-0022-N0)
Posted date 2021年7月28日
Country 世界知的所有権機関(WIPO)
International application number 2020JP040071
International publication number WO 2021080020
Date of international filing 令和2年10月26日(2020.10.26)
Date of international publication 令和3年4月29日(2021.4.29)
Priority data
  • 特願2019-194646 (2019.10.25) JP
Title NUCLEIC ACID DELIVERY ENHANCER
Abstract Provided is a novel anti-tumor agent capable of delivering siRNA or shRNA specifically to pancreatic cancer cells and suppressing tumor enlargement, infiltration, and metastasis of pancreatic cancer. The present invention provides a nucleic acid delivery enhancer that is for delivering siRNA or shRNA into cells and that comprises a folate-cationic oligopeptide complex. The present invention also provides an anti-tumor agent that contains a folate-cationic oligopeptide complex and siRNA or shRNA capable of binding to mRNA or snoRNA expressed in pancreatic cancer cells to inhibit the expression. Said siRNA is capable of binding to RNA selected from the group consisting of, for example, SNORA18 snoRNA, NUP85 mRNA, WASF2 mRNA, and SNORA22 snoRNA.
Outline of related art and contending technology BACKGROUND ART
Pancreatic cancer is said to be the worst prognostic among cancers. The reason for this is that early detection is difficult because the pancreas is a retroperitoneal organ, and the mobility of pancreatic cancer cells is extremely high, so that there is a strong tendency for peritoneal infiltration and metastasis to blood vessels, gastrointestinal tract, nerves, and the like.
In investigating the mechanisms of pancreatic cancer infiltration and metastasis, the present inventors have previously been found in the karyotes; Insulin-like growth factor 2mRNA binding protein 3 (Insulin-like Growth Factor 2 mRNA-Binding Protein 3, which is known to bind to the 5 ' untranslated region of insulin-like growth factor II mRNA and inhibit translation of insulin-like growth factor II; It has been found that IGF2BP3) is present in the cell membrane process in pancreatic cancer cells, and that various mRNA binds to this IGF2BP3 and accumulates in the cell membrane process. It has also been reported that inhibition of these mRNA by RNA interference (RNAi) effectively suppresses pancreatic cancer cell infiltration and metastasis (Patent Document 1).
siRNA (small interfering RNA), which is representative of nucleic acid medicine utilizing RNA interference (RNAi), which has recently attracted attention as a new therapeutic agent, is a small double-stranded RNA, which generally consists of 21 ~ 23 base pairs. However, siRNA has been problematic in terms of delivery into cells due to its high anionic nature and low cell membrane permeability due to its structure. To address this problem, the present inventors have previously produced a siRNA-folic acid-polyethylene glycol (PEG)-chitosan oligosaccharide-lactic acid (COL) nanoparticle complex and confirmed the effect of these nanoparticles on promoting uptake of siRNA into cells. It has also been reported that siRNA to mRNA having the ability to bind IGF2BP3 taken up by pancreatic cancer cells suppresses pancreatic cancer infiltration and metastasis (NpL 1).
On the other hand, the present inventors have found that a cationic oligopeptide having an amino group or guanidino group on a side chain is useful for delivery of double-stranded RNA into a cell (Patent Document 2, Non-Patent Document 2). In addition, in order to deliver RNAi molecules, the use of complexes containing vitamin E and a cationic sugar has also been studied (NpL 3 and 4).
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • KOCHI UNIVERSITY
  • TOKYO UNIVERSITY OF SCIENCE FOUNDATION
  • Inventor
  • TANIUCHI Keisuke
  • WADA Takeshi
  • HARA Rintaro
  • SATO Kazuki
  • TAKAGI Kazunori
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS IT JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN WS ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
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