Highly efficient and specific gene transfer to Purkinje cells in vivo using a herpes simplex virus I amplicon

Human Gene Therapy
Marta AgudoFrancisco Wandosell

Abstract

The transduction of cerebellar neurons in vivo with herpes simplex virus 1 (HSV-1) amplicon carrying the lacZ gene has been investigated after injection of the vector in the cerebellar cortex, ventricles, and inferior olive of adult rats. Injection into the cerebellar cortex resulted in transduction of Purkinje cells near the needle tract and injection into the ventricles yielded no transduced neurons. In contrast, high transduction efficiency was achieved by vector injection into the inferior olive, resulting in one of three positive Purkinje cells all over the ipsilateral and contralateral cerebellar hemispheres. Because neurons in the deep cerebellar nuclei are also transduced, we suggest that the vector is delivered from the inferior olive to the cerebellar nuclei and then to Purkinje cells by retrograde axonal transport. Expression of the lacZ gene within Purkinje cells was surprisingly persistent and was maintained at the same level for at least 40 days. Importantly, no signs of either toxicity or inflammation were observed in the cerebellum after vector injection, except for the borders of the needle tract where some reactive astrocytes were detected. Indeed, motor coordination of treated animals was entirely normal, as ...Continue Reading

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Citations

Jul 17, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Michele M P LufinoRichard Wade-Martins
Jan 20, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Silvia Gomez-SebastianRichard Wade-Martins
Mar 22, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Filip LimJavier Díaz-Nido
Sep 24, 2010·Journal of Biomedicine & Biotechnology·Sara Pérez-Luz, Javier Díaz-Nido
Aug 12, 2010·The Cerebellum·Jean-Pierre LouboutinDavid S Strayer
Aug 2, 2007·Expert Opinion on Biological Therapy·Delphine CuchetAlberto L Epstein
Jul 14, 2006·The European Journal of Neuroscience·Takashi TorashimaHirokazu Hirai
Jul 11, 2012·The European Journal of Neuroscience·Jun NishiyamaMichisuke Yuzaki
Sep 23, 2006·Neurochemistry International·Alfredo Gimenez-CassinaJavier Diaz-Nido
Mar 7, 2006·Brain Research·Takashi TorashimaHirokazu Hirai
Sep 29, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Angelika OehmigXandra O Breakefield
Oct 13, 2009·Neurochemical Research·Masahiko Tanaka

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