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LIPID MEMBRANE STRUCTURE HAVING INTRANUCLEAR LOCALIZATION PROPERTY

外国特許コード F150008584
整理番号 (S2014-0299-N0)
掲載日 2015年11月26日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2014JP084034
国際公開番号 WO 2015098907
国際出願日 平成26年12月24日(2014.12.24)
国際公開日 平成27年7月2日(2015.7.2)
優先権データ
  • 特願2013-264927 (2013.12.24) JP
発明の名称 (英語) LIPID MEMBRANE STRUCTURE HAVING INTRANUCLEAR LOCALIZATION PROPERTY
発明の概要(英語) A lipid membrane structure for delivering a substance into the nucleus of a cell. The lipid membrane structure can deliver a nucleic acid into the nucleus of an immunocyte such as a dendritic cell with high efficiency. In the lipid membrane structure, a lipid membrane is modified with (a) a polypeptide which comprises the amino acid sequence represented by SEQ ID NO: 1 and/or (b) a polypeptide which comprises an amino acid sequence produced by the deletion and/or substitution and/or insertion of one or several amino acid residues in the amino acid sequence represented by SEQ ID NO: 1 and which has an activity of promoting the migration of the lipid membrane structure into the nucleus of a cell.
従来技術、競合技術の概要(英語) BACKGROUND ART
An agent that specifically binds to the affected area as a means of transporting the lipid membrane structure encapsulating the drug in liposomes has been proposed a method. In particular, the treatment of malignant tumors in the field of anti-tumor agent is encapsulated in the liposomes and the effectiveness of many reported. In addition, the lipid membrane structure can be used for gene expression as a multifunctional envelope-type nano-structures (MEND: Multifunctional envelope-type nano device; hereinafter, is abbreviated as' MEND ' herein. Such as for example see Drug Delivery System, 22-2, pp.115-122, 2007) is proposed. This structure may be, selectively in a particular cell such as a gene for the delivery of a drug delivery system can be used as, for example, such as gene therapy of the tumor has been known to be useful.
The structure may be used lipid membrane drug, nucleic acid, peptide, polypeptide, or the target substance such as sugars such as tumor specific target organ site as a means for delivery, the surface of the lipid membrane structure is modified with functional molecules have been proposed many methods. Of an agent such as an anti-tumor agent containing a lipid membrane structure is a target cell by endocytosis and reaches into the cell to be contained within endosomes and the state is, then, enzymatic hydrolysis of lysosomes in response to the action or the like included in the drug has been released into the cytoplasm. Has been absorbed in the endosome in order to improve the drug release from the liposome, the surface of the liposome to the peptide (GALA: modified MEND Biochemistry, 26, pp.2964-2972, 1987) (Biochemistry, 43, pp.5618-5623, 2004) or liposome (Japanese Patent Application JP-2006-28030) is proposed.
In addition, nucleic acid and the like of a target substance containing a lipid film structure is transferred into the nucleus of the target cell as means for, for example, the external surface of the liposome in the liposome octaarginine (International Publication WO2005/32593; Journal of Controlled Release, 98, pp.317-323, 2004), nuclear translocation peptide modified liposomes having a lipid membrane layer membrane 2 (International Publication WO2006/101201), of monosaccharides such as galactose or mannose surface of the liposome (International Publication WO2007/102481) is proposed. Multiple lipid membrane modified saccharide structure (T-MEND) is fuzed to a lipid membrane and nuclear membranes and shows, in vitro gene expression in the test result was improved efficiency thereof.
On the other hand, immune cells, in particular antigen presenting dendritic cells has the effect of an antigenic protein in the nucleus of introducing a nucleic acid encoding it, which is transcribed and translated from the nucleic acids in dendritic cells and the antigen-presenting dendritic cell surface protein can be, immunity against the proteins with the living body can be obtained. From this point of view, an immune cell such as dendritic nucleic acid in the nucleus of a technique for efficient delivery is demanded.
However, such as a lipid membrane structure described above using MEND dendritic cells in the nucleus of acid in the case of introducing a nucleic acid introduction efficiency is, other cells, for example tumor cells and compared with the case of hepatocytes is not sufficient. Finally the introduced nucleic acid expression in the nucleus until, uptake into, endosomal escape, nuclear import, nuclear transcription and a variety of intracellular kinetics is need to undergo processes, non-dividing cells such as dendritic cells in a core film layer membrane 2 is always present and intact, the nuclear envelope lipid membrane structure does not block the ability of the nuclear import is conjectured. Therefore, the structure may be used lipid membrane to the nucleus of dendritic cells in order to deliver nucleic acids, each of the above processes, in particular a core-layer membrane 2 how to break through the barrier film is to be, extremely becomes an important problem.
27 Peptide KALA polypeptide referred to as amino acid residues are known and, using the plasmid DNA itself cationic charge can be forming a complex have been reported (Biochemistry, 36, pp.3008-3017, 1997). This peptide KALA liposomes lipid membrane by modifying the surface of the structure of the lipid membrane structure could promote nuclear import (International Publication WO 2011/132713) have been reported.
  • 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
  • NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITY
  • 発明者(英語)
  • HARASHIMA Hideyoshi
  • AKITA Hidetaka
  • MIURA Naoya
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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