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Molecular, Biochemical, and Genetic Techniques

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Systemic delivery of an AAV vector in neonatal macaques facilitates widespread gene transduction into neurons throughout the brain

  • P2-383
  • 井上 謙一 / Kenichi Inoue:1 木村 活生 / Katsuo Kimura:1,2 安河内 竜二 / Ryuji Yasukochi:1 菅原 直也 / Naoya Sugawara:1 小笠原 宇弥 / Takaya Ogasawara:1 奥田 泰弘 / Yasuhiro Okuda:1 藤原 真紀 / Maki Fujiwara:1 高田 昌彦 / Masahiko Takada:1 
  • 1:京都大学霊長類研究所 統合脳システム分野 / Sys Neurosci Sec, Primate Res Inst, Kyoto Univ, Inuyama, Japan 2:横浜市立大学・医・神経内科 / Dept Neurol and Stroke Med, Yokohama City Univ, Yokohama, Japan 

Recombinant adeno-associated virus (AAV) vectors provide a powerful tool for delivering target genes into the brain. Recent studies demonstrated that serotype 9 of AAV (AAV9) was able to cross the blood-brain barrier, and that systemic administration of self-complementary AAV9 vector to neonatal mice, rats, and cats resulted in efficient gene transduction into neurons. However, no successful gene transduction into neurons has yet been performed in neonatal non-human primates. Here we show that systemic delivery of a single-stranded AAV9 vector in neonatal macaques facilitated widespread gene transduction into neurons throughout the brain. We injected 1.0 x 1014 viral genome/kg of the AAV vector expressing green fluorescent protein (GFP) under CMV promoter control via the saphenous vein. Robust GFP expression was observed in both neurons and glia over the cerebral cortex, subcortical structures, and cerebellum. Neuronal tropism and transduction efficiency varied depending on the brain region and cell type. Purkinje cells in the cerebellar cortex displayed the highest transduction efficiency. The present results indicate that systemic delivery of the AAV9 vector in neonatal macaques is a potential methodology to transduce target genes efficiently throughout the brain and is useful in creating genetically manipulated primate models for neuropsychiatric diseases and developing their gene therapeutic approaches.

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