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Publication Detail
In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression
  • Publication Type:
    Journal article
  • Publication Sub Type:
    JOUR
  • Authors:
    Rahim AA, Wong AM, Ahmadi S, Hoefer K, Buckley SM, Hughes DA, Nathwani AN, Baker AH, McVey JH, Cooper JD, Waddington SN
  • Publication date:
    10/11/2011
  • Journal:
    Gene Ther.
  • Author URL:
  • Notes:
    DA - 20111110 IS - 1476-5462 (Electronic) IS - 0969-7128 (Linking) LA - ENG PT - JOURNAL ARTICLE
Abstract
The efficient delivery of genetic material to the developing fetal brain represents a powerful research tool and a means to supply therapy in a number of neonatal lethal neurological disorders. In this study, we have delivered vectors based upon adenovirus serotype 5 (Ad5) and adeno-associated virus (AAV) pseudotypes 2/5, 2/8 and 2/9 expressing green fluorescent protein to the E16 fetal mouse brain. One month post injection, widespread caudal to rostral transduction of neural cells was observed. In discrete areas of the brain these vectors produced differential transduction patterns. AAV2/8 and 2/9 produced the most extensive gene delivery and had similar transduction profiles. All AAV pseudotypes preferentially transduced neurons whereas Ad5 transduced both neurons and glial cells. None of the vectors elicited any significant microglia-mediated immune response when compared with control uninjected mice. Whole-body imaging and immunohistological evaluation of brains 9 months post injection revealed long-term expression using these non-integrating vectors. These data will be useful in targeting genetic material to discrete or widespread areas of the fetal brain with the purpose of devising therapies for early neonatal lethal neurodegenerative disease and for studying brain development.Gene Therapy advance online publication, 10 November 2011; doi:10.1038/gt.2011.157
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