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MOLECULAR ASSEMBLY CONTAINING MODIFIED RNA, AND RNA DELIVERY SYSTEM USING SAME

外国特許コード F160008828
整理番号 (S2015-0127-N0)
掲載日 2016年8月10日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2015JP081352
国際公開番号 WO 2016072500
国際出願日 平成27年11月6日(2015.11.6)
国際公開日 平成28年5月12日(2016.5.12)
優先権データ
  • 特願2014-227611 (2014.11.8) JP
発明の名称 (英語) MOLECULAR ASSEMBLY CONTAINING MODIFIED RNA, AND RNA DELIVERY SYSTEM USING SAME
発明の概要(英語) The present invention principally addresses the problem of providing a novel molecular assembly containing functional RNA and capable of introducing functional RNA such as siRNA and shRNA into a cell by in vivo administration, and also delivering the functional RNA to a diseased site. The present invention provides, for example, a molecular assembly characterized by containing the following as essential components thereof: an amphiphilic block polymer A having a hydrophilic block containing a sarcosine chain and a hydrophobic block containing a lactic acid chain; RNA modified by a compound having a long-chain hydrophobic group such as a polylactic acid chain or a polylactic acid-polysarcosine copolymer chain; a plasma-membrane-binding compound (CPP, etc.); and a photosensitizer which may bond to one or more of these components. The present invention is useful as an RNA delivery system (DDS) into tumor cytoplasm and as a cancer preventive or therapeutic agent.
特許請求の範囲(英語) [claim1]
1. It features that it includes the component of statement in the following 1-4 as necessity, the molecular aggregate.
1) The parents crocking characteristic block polymer A which possesses with the hydrophilic block which includes the sarcosine chain and the hydrophobic block which includes the lactic acid chain
2) RNA which is decorated by the chemical compound which possesses the long chain hydrophobic radical
3) Cell membrane connection characteristic chemical compound
4) The photosensitizer which it is possible to have connected to the component of one or more of the above-mentioned 1-3.
[claim2]
2. Parents crocking characteristic block polymer A, is something which possesses with the hydrophilic block to which the 20-300 includes the sarcosine unit and the hydrophobic block to which the 10-100 includes the lactic acid unit, in claim 1 the molecular aggregate of statement.
[claim3]
3. The chemical compound which possesses the long chain hydrophobic radical, poly- lactic acid and poly- lactic acid [porisarukoshinkoporima] or [jimetokishitorichiruokishi] - is [hekishirujichiohekisan], in claim 1 or 2 the molecular aggregate of statement.
[claim4]
4. Poly- lactic acid or the poly- lactic acid of poly- lactic acid [porisarukoshinkoporima], the 10-60 consists of the lactic acid unit, poly- sarcosine, is something where the 0-100 consists of the sarcosine unit, in claim 3 the molecular aggregate of statement.
[claim5]
5. RNA, is something which possesses the gene revelation depression effect, either of the claim 1-4 in one section the molecular aggregate of statement.
[claim6]
6. RNA which possesses the gene revelation depression effect, is siRNA, shRNA, miRNA, anti sense RNA, [aputama] RNA and [ribozaimu], in claim 5 the molecular aggregate of statement.
[claim7]
7. It is siRNA which knocks down siRNA, or the [huerokerataze] gene where SiRNA, ATP-binding cassette transporter G2 (ABCG2) knocks down the gene, controls the revelation, obstructs the activity, or is the both combined use ones, in claim 6 the molecular aggregate of statement.
[claim8]
8. SiRNA which knocks down the ABCG2 gene, controls the revelation, is two these chain nuclear acids which consist of the next sense chain and the anti sense chain, in claim 7 the molecular aggregate of statement.
Sense chain (arrangement number 10):
5' - CGAUAUGGAUUUACGGCUUdTdT-3'
Anti sense chain (arrangement number 11):
5' - AAGCCGUAAAUCCAUAUCGdTdG-3'
[claim9]
9. SiRNA which knocks down the [huerokerataze] gene, obstructs the activity, is two these chain nuclear acids which consist of the next sense chain and the anti sense chain, in claim 7 the molecular aggregate of statement.
Sense chain (arrangement number 12):
5' - GCAUUUACCAGUGACCAUAdTdT-3'
Anti sense chain (arrangement number 13):
5' - UAUGGUCACUGGUAAAUGCdTdA-3'
[claim10]
10. Cell membrane connection characteristic chemical compound, is cell membrane permeable peptide, either of the claim 1-9 in one section the molecular aggregate of statement.
[claim11]
11. Cell membrane permeable peptide,
Arrangement number 1: GALFLGFLGAAGSTMGAWSQPKKKRKV
Arrangement number 2: YGRKKRRQRRRG
Arrangement number 3: RRRRNRTRRNRRRVR
Arrangement number 4: YGRRARRRRRRR
Arrangement number 5: KETWWETWWTE
Arrangement number 14: RKKRRRESRKKRRRESC
Arrangement number 15: YARAAARQARAC
Arrangement number 16: KETWWETWWTEWSQPKKKRKVC, or
Arrangement number 17: LIRLWSHLIHIWFQNRRLKWKKKC
So it is, in claim 10 the molecular aggregate of statement.
[claim12]
12. The photosensitizer, is something which functioning is done with the light which possesses the wave length of 450nm-1300nm, either of the claim 1-11 in one section the molecular aggregate of statement.
[claim13]
13. The photosensitizer which functioning is done, cyanine type pigment, the rhodamine type pigment such as fluorescein pigment and the Indian cyanine pigment and the porphyrin pigment, Alexa Fluor (registered trade mark) 546, Alexa Fluor (registered trade mark) 633, Alexa Fluor (registered trade mark) 750, DY750, DY751, DY780 and the eosin, rose Bengal, IRDye (registered trade mark) 800CW and [karubokishihuruoresein] (FAM) is with the light which possesses the wave length of 450nm-1300nm, in claim 12 the molecular aggregate of statement.
[claim14]
14. Particle diameter is 10-100nm, either of the claim 1-13 in one section the molecular aggregate of statement.
[claim15]
15. Either of the claim 1-14 it features that the molecular aggregate of statement is used for one section, the RNA delivery system to inside the tumor cytoplasm.
[claim16]
16. Either of the claim 1-14 it features that the molecular aggregate of statement is included in one section, the preventive medicine or the remedy medicine of the cancer.
[claim17]
17. The device which has the expedient which irradiates the excited light because the preventive medicine or the remedy medicine of statement, and the photosensitizer in the molecular aggregate which is included in that are made to excite to claim 16 is included, the preventive of the cancer or remedy system.
[claim18]
18. Prescribing the preventive medicine or the remedy medicine of statement to in vivo in claim 16, and the fact that excited light because the photosensitizer in the molecular aggregate which is included in the preventive medicine or the remedy medicine which is prescribed is made to excite is irradiated is included, preventive method or remedy method of the cancer.
[claim19]
19. RNA which is decorated poly- lactic acid or by the macromolecule which possesses poly- lactic acid [porisarukoshinkoporima].
[claim20]
20. RNA, is something which possesses the gene revelation depression effect, in claim 19 RNA of statement.
[claim21]
21. RNA which possesses the gene revelation depression effect, is siRNA, shRNA, miRNA, anti sense RNA, [aputama] RNA and [ribozaimu], in claim 20 RNA of statement.
[claim22]
22. It is siRNA which knocks down siRNA, or the [huerokerataze] gene where SiRNA, ATP-binding cassette transporter G2 (ABCG2) knocks down the gene, controls the revelation, obstructs the activity, or is the both combined use ones, in claim 21 RNA of statement.
[claim23]
23. SiRNA which knocks down the ABCG2 gene, controls the revelation, is two these chain nuclear acids which consist of the next sense chain and the anti sense chain, in claim 22 RNA of statement.
Sense chain (arrangement number 10):
5' - CGAUAUGGAUUUACGGCUUdTdT-3'
Anti sense chain (arrangement number 11):
5' - AAGCCGUAAAUCCAUAUCGdTdG-3'
[claim24]
24. SiRNA which knocks down the [huerokerataze] gene, obstructs the activity, is two these chain nuclear acids which consist of the next sense chain and the anti sense chain, in claim 22 RNA of statement.
Sense chain (arrangement number 12):
5' - GCAUUUACCAGUGACCAUAdTdT-3'
Anti sense chain (arrangement number 13):
5' - UAUGGUCACUGGUAAAUGCdTdA-3'
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • OKAYAMA UNIVERSITY
  • SHIMADZU CORPORATION
  • 発明者(英語)
  • OHTSUKI TAKASHI
  • MATSUURA EIJI
  • KOBUCHI HIROTSUGU
  • AKAHOSHI AKIYA
  • OZEKI EIICHI
国際特許分類(IPC)
指定国 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 DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR 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 SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN 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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