TY  - JOUR
A1  - Counsell, John R.
A1  - Karda, Rajvinder
A1  - Diaz, Juan Antiano
A1  - Carey, Louise
A1  - Wiktorowicz, Tatiana
A1  - Buckley, Suzanne M. K.
A1  - Ameri, Shima
A1  - Ng, Joanne
A1  - Baruteau, Julien
A1  - Almeida, Filipa
A1  - de Silva, Rohan
A1  - Simone, Roberto
A1  - Lugarà, Eleonora
A1  - Lignani, Gabriele
A1  - Lindemann, Dirk
A1  - Rethwilm, Axel
A1  - Rahim, Ahad A.
A1  - Waddington, Simon N.
A1  - Howe, Steven J.
T1  - Foamy Virus Vectors Transduce Visceral Organs and Hippocampal Structures following In Vivo Delivery to Neonatal Mice
JF  - Molecular Therapy: Nucleic Acids
N2  - 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.
KW  - foamy virus
KW  - spumavirus
KW  - viral vector
KW  - gene therapy
KW  - vector tropism
KW  - bioimaging
KW  - hippocampus
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223379
VL  - 12
ER  -