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Mol Ther Nucleic Acids. 2018 Sep 7;12:626-634. doi: 10.1016/j.omtn.2018.07.006. Epub 2018 Aug 3.

Foamy Virus Vectors Transduce Visceral Organs and Hippocampal Structures following In Vivo Delivery to Neonatal Mice.

Author information

1
Gene Transfer Technology Group, EGA Institute for Women's Health, University College London, London WC1E 6HX, UK; Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, 30 Guilford Street, London WC1N 1EH, UK.
2
Gene Transfer Technology Group, EGA Institute for Women's Health, University College London, London WC1E 6HX, UK.
3
Universität Würzburg, Institut für Virologie und Immunbiologie, Versbacher Str. 7, 97078 Würzburg, Germany.
4
Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK.
5
Department of Clinical and Experimental Epilepsy, Queen Square House, UCL Institute of Neurology, London WC1N 3BG, UK.
6
Universität Würzburg, Institut für Virologie und Immunbiologie, Versbacher Str. 7, 97078 Würzburg, Germany; Institute of Virology, Technische Universität Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.
7
Department of Pharmacology, UCL School of Pharmacy, University College London, London WC1N 1AX, UK.
8
Gene Transfer Technology Group, EGA Institute for Women's Health, University College London, London WC1E 6HX, UK; Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: s.waddington@ucl.ac.uk.

Abstract

Viral vectors are rapidly being developed for a range of applications in research and gene therapy. Prototype foamy virus (PFV) vectors have been described for gene therapy, although their use has mainly been restricted to ex vivo stem cell modification. Here we report direct in vivo transgene delivery with PFV vectors carrying reporter gene constructs. In our investigations, systemic PFV vector delivery to neonatal mice gave transgene expression in the heart, xiphisternum, liver, pancreas, and gut, whereas intracranial administration produced brain expression until animals were euthanized 49 days post-transduction. Immunostaining and confocal microscopy analysis of injected brains showed that transgene expression was highly localized to hippocampal architecture despite vector delivery being administered to the lateral ventricle. This was compared with intracranial biodistribution of lentiviral vectors and adeno-associated virus vectors, which gave a broad, non-specific spread through the neonatal mouse brain without regional localization, even when administered at lower copy numbers. Our work demonstrates that PFV can be used for neonatal gene delivery with an intracranial expression profile that localizes to hippocampal neurons, potentially because of the mitotic status of the targeted cells, which could be of use for research applications and gene therapy of neurological disorders.

KEYWORDS:

bioimaging; foamy virus; gene therapy; hippocampus; spumavirus; vector tropism; viral vector

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