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RETROGRADE TRANSPORT VIRAL VECTOR SYSTEM HAVING ENVELOPE COMPRISING FUSED GLYCOPROTEIN UPDATE

外国特許コード F110003181
整理番号 A301-01WO
掲載日 2011年6月22日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2010JP070136
国際公開番号 WO 2011068019
国際出願日 平成22年11月11日(2010.11.11)
国際公開日 平成23年6月9日(2011.6.9)
優先権データ
  • 特願2009-274156 (2009.12.2) JP
発明の名称 (英語) RETROGRADE TRANSPORT VIRAL VECTOR SYSTEM HAVING ENVELOPE COMPRISING FUSED GLYCOPROTEIN UPDATE
発明の概要(英語) Provided is a lentiviral vector system which sustains a high-frequency retrograde transportation ability in animal brain and has a higher titer. A kit for preparing a retrograde transport viral vector, which comprises: (1) a packaging plasmid containing the gag gene and pol gene of HIV-1; (2) a packaging plasmid containing an accessory gene of HIV-1; (3) a transfer plasmid containing a target gene; and (4) an envelope plasmid containing, as an envelope gene, a gene encoding a fused polypeptide comprising the extracellular domain of rabies virus glycoprotein (RV-G), the transmembrane domain of rabies virus glycoprotein (RV-G) or vesicular stomatitis virus glycoprotein (VSV-G) and the intracellular domain of vesicular stomatitis virus glycoprotein (VSV-G).
従来技術、競合技術の概要(英語) BACKGROUND ART
Non-proliferating (non-replicating) type recombinant vectors is, a gene of interest in the central nervous system (CNS) transport non-dividing cells and maintain the expression system over the long term gene therapy for various diseases such as many as vectors for used in the study (non-patent document 1-4). In particular, vectors derived from primate HIV-1 (human immunodeficiency virus type 1) as vectors for gene therapy is of value that the best (non-patent document 5-8).
On the other hand, certain gene for for the treatment of neurodegenerative disorders, nerve endings in the infected site, transported in a retrograde fashion axons, such infection site located at a remote location at the target site is a gene of interest is introduced into the cell body can be a viral vector (Fig. 1) is beneficial.
So far, as the envelope glycoprotein (envelope gene protein), vesicular stomatitis virus (vesicular stomatitis virus: VSV) glycoprotein (VSV-G) (pseudotyped: pseudotyped) using recombinant virus using HIV-1, cynomolgus retrograde transport in the brain has been systems have been developed, retrograde transport of this vector is efficient (non-patent document 9) is not. In the method described in this document, the result was confirmed by immunostaining, injected to the striatum of the monkey recombinant HIV-1 in a retrograde fashion viruses in infected cells of the central nervous system had a slight.
On the other hand, rabies virus (rabies virus: RV) is, more infected the synaptic terminal, transported in a retrograde fashion axons activity that is known. In fact, equine anemia virus RV-G by retrograde transport of a non-primate vectors based on the ability is increased by have been reported (non-patent document 10, patent document 1 and 11).
Further, RV-G pseudotyped lentiviral HIV-1 was reported (non-patent document 3) but, in practice this report in an animal experiment (in vivo) using viral vectors is not performed. In addition, cause the nerves of rabies virus in a one-way, or glycoprotein (Mokola lyssavirus) moko larissa virus VSV-G pseudotyped HIV-1 and gene transfer vectors have been studied in the CNS. Glycoprotein or moko larissa virus pseudotyped with the VSV-G vector was injected into the rats nostril HIV-1 as a result, with respect to retrograde transport to the olfactory system, these vectors can be comparable to each other (non-patent document 12). In addition, this document discloses that the viral vector was administered via the striatum has not been described the.
The present inventors have thus far, of the rabies virus glycoprotein gene (RV-G) lentiviruses pseudotyped HIV-1 in vector (vector RV-G/HIV-1) thus produced, various high frequency can be in the region in the brain to allow retrograde gene transfer revealed (Patent Document 2, Hum. Gene Ther., 2007).
  • 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
  • Japan Science and Technology Agency
  • 発明者(英語)
  • KOBAYASHI Kazuto
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH 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 IS KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PE PG PH PL PT RO RS RU 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 SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD 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 ML MR NE SN TD TG
参考情報 (研究プロジェクト等) CREST 脳の機能発達と学習メカニズムの解明 領域
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