Abstract
We attempted in vivo gene transfection into the central nervous system (CNS) of non-human primates using the hemagglutinating virus of Japan (HVJ)-AVE liposome, a newly constructed anionic type liposome with a lipid composition similar to that of HIV envelopes and coated by the fusogenic envelope proteins of inactivated HVJ. HVJ-AVE liposomes containing the lacZ gene were applied intrathecally through the cisterna magna of Japanese macaques. Widespread transgene expression was observed mainly in the neurons. The lacZ gene was highly expressed in the medial temporal lobe, brainstem, Purkinje cells of cerebellar vermis and upper cervical cord (29.0 to 59.4% of neurons). Intrastriatal injection of an HVJ-AVE liposome–lacZ complex made a focal transfection around the injection sites up to 15 mm. We conclude that the infusion of HVJ-AVE liposomes into the cerebrospinal fluid (CSF) space is applicable for widespread gene delivery into the CNS of large animals.
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Acknowledgements
We greatly appreciate the technical support of Ichiro Fujita, Hiroyuki Yoneshima, Hisashi Tanigawa and Keisuke Kawasaki, Laboratory of Cognitive Neuroscience, Department of Biophysical engineering, Osaka University Graduate School of Engineering Science.
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Hagihara, Y., Saitoh, Y., Kaneda, Y. et al. Widespread gene transfection into the central nervous system of primates. Gene Ther 7, 759–763 (2000). https://doi.org/10.1038/sj.gt.3301169
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DOI: https://doi.org/10.1038/sj.gt.3301169
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