分子ZIPコード標識による超ウイルスベクターを用いたピンポイント遺伝子輸送（第9回基礎・臨床融合の学内共同研究発表会）（抄録）

IR

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  • Super viral vector for pinpoint gene transfer by molecular ZIP-code
  • ブンシ ZIP コード ヒョウシキ ニ ヨル チョウ ウイルス ベクター ヲ モチイタ ピンポイント イデンシ ユソウ （ダイ 9カイ キソ リンショウ ユウゴウ ノ ガクナイ キョウドウ ケンキュウ ハッピョウカイ）（ショウロク）

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Abstract

type:Departmental Bulletin Paper

Molecular ZIP-code is very small size of peptide, which be able to target to specific tissues or cells, recently considered as one of theremarkable material for molecular imaging or therapy. In this study, we engineered the new therapeutic strategy to realize pinpoint genetransfer with Molecular ZIP-code inserted into helper-dependent adenovirus vectors (HDAd). We identified three different types of dorsalroot ganglion (DRG) Molecular ZIP-code which could specifically bind to DRG neurons. Each ZIP-code were separately inserted into thefiber of helper virus detargeted for its native tropism (coxsackie and adenovirus receptor and heparan sulfate proteoglycan binding site). Wegenerated the DRG-targeting HDAd with the use of DRG-targeting helper virus, injected the HDAd into intrathecal lesion of mice andevaluated the transduction efficiency. Most effective HDAd produced a 100-fold higher transduction of DRG neurons than non-targetingvector and three different kinds of DRG-targeting HDAd showed the different transduction patterns in the cell size distribution of DRGneurons. We succeeded to develop a new strategy to produce HDAd that specifically target DRG neurons. The development of the strategy inthis communication using the much more versatile and far less toxic HDAd should facilitate its possible application in clinical trials for DRGneuronopathies in the near future.

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