foamy virus vectors transduce visceral organs and hippocampal structures following in vivo delivery to neonatal mice
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ID: 147491
2018
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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: foamy virus, spumavirus, viral vector, gene therapy, vector tropism, bioimaging, hippocampus
| Reference Key |
counsell2018molecularfoamy
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| Authors | ;John R. Counsell;Rajvinder Karda;Juan Antinao Diaz;Louise Carey;Tatiana Wiktorowicz;Suzanne M.K. Buckley;Shima Ameri;Joanne Ng;Julien Baruteau;Filipa Almeida;Rohan de Silva;Roberto Simone;Eleonora Lugarà;Gabriele Lignani;Dirk Lindemann;Axel Rethwilm;Ahad A. Rahim;Simon N. Waddington;Steven J. Howe |
| Journal | coordination chemistry reviews |
| Year | 2018 |
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