Efficient transduction of 11 poly-arginine peptide in an ischemic lesion of mouse brain

Yuki Gotanda, Fan Yan Wei, Hideki Harada, Keisuke Ohta, Kei Ichiro Nakamura, Kazuhito Tomizawa, Kazuo Ushijima

    Research output: Contribution to journalArticlepeer-review

    9 Citations (Scopus)

    Abstract

    Direct intracellular delivery of intact proteins has been successfully achieved by tagging cell-penetrating peptide (CPP), which consists of short positively charged amino acids, such as 11 poly-arginine (11R); however, in vivo delivery of the proteins to the brain has remained challenging because it is unclear whether CPP would enable proteins to cross the blood-brain barrier (BBB). In this study, we conducted an in vivo kinetic study to investigate the efficiency of 11R-mediated peptide delivery in the normal and ischemic brain. The 11R was observed in the microvessels and neurons surrounding the microvessels throughout the brain 1 hour after systemic administration, but the signal of the peptide was faint after 2 hours. In a transient middle cerebral artery occlusion mouse model, 11R was markedly enhanced and remained detectable in the cells on the ipsilateral side for as long as 8 hours after administration compared with the contralateral side. These results suggest that 11R is capable of in vivo delivery to the brain by passing through the BBB. Furthermore, 11R-mediated protein transduction could be used for the delivery of therapeutic molecules in cerebral ischemia.

    Original languageEnglish
    Pages (from-to)2023-2030
    Number of pages8
    JournalJournal of Stroke and Cerebrovascular Diseases
    Volume23
    Issue number8
    DOIs
    Publication statusPublished - Sep 1 2014

    Keywords

    • Protein transduction
    • brain
    • ischemia
    • poly-arginine

    ASJC Scopus subject areas

    • Surgery
    • Rehabilitation
    • Clinical Neurology
    • Cardiology and Cardiovascular Medicine

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