In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the trigeminal ganglia
Abstract The ability to genetically manipulate trigeminal ganglion (TG) neurons would be useful in the study of the craniofacial nervous system and latent alphaherpesvirus infections. We investigated adeno-associated virus (AAV) vectors for gene delivery to the TG after intradermal whiskerpad delive...
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2017-04-01
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doaj-b68a60e4420041afb93d1660c83fed5e2020-12-08T03:15:49ZengNature Publishing GroupScientific Reports2045-23222017-04-017111310.1038/s41598-017-01004-yIn vivo dynamics of AAV-mediated gene delivery to sensory neurons of the trigeminal gangliaChung H. Dang0Martine Aubert1Harshana S. De Silva Feelixge2Kurt Diem3Michelle A. Loprieno4Pavitra Roychoudhury5Daniel Stone6Keith R. Jerome7Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research CenterDepartment of Laboratory Medicine, University of WashingtonVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research CenterVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research CenterAbstract The ability to genetically manipulate trigeminal ganglion (TG) neurons would be useful in the study of the craniofacial nervous system and latent alphaherpesvirus infections. We investigated adeno-associated virus (AAV) vectors for gene delivery to the TG after intradermal whiskerpad delivery in mice. We demonstrated that AAV vectors of serotypes 1, 7, 8, and 9 trafficked from the whiskerpad into TG neurons and expressed transgenes within cell bodies and axons of sensory neurons in all three branches of the TG. Gene expression was highest with AAV1, and steadily increased over time up to day 28. Both constitutive and neuronal-specific promoters were able to drive transgene expression in TG neurons. Levels of vector genomes in the TG increased with input dose, and multiple transgenes could be co-delivered to TG neurons by separate AAV vectors. In conclusion, AAV1 vectors are suitable for gene delivery to TG sensory neurons following intradermal whiskerpad injection.https://doi.org/10.1038/s41598-017-01004-y |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chung H. Dang Martine Aubert Harshana S. De Silva Feelixge Kurt Diem Michelle A. Loprieno Pavitra Roychoudhury Daniel Stone Keith R. Jerome |
spellingShingle |
Chung H. Dang Martine Aubert Harshana S. De Silva Feelixge Kurt Diem Michelle A. Loprieno Pavitra Roychoudhury Daniel Stone Keith R. Jerome In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the trigeminal ganglia Scientific Reports |
author_facet |
Chung H. Dang Martine Aubert Harshana S. De Silva Feelixge Kurt Diem Michelle A. Loprieno Pavitra Roychoudhury Daniel Stone Keith R. Jerome |
author_sort |
Chung H. Dang |
title |
In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the trigeminal ganglia |
title_short |
In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the trigeminal ganglia |
title_full |
In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the trigeminal ganglia |
title_fullStr |
In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the trigeminal ganglia |
title_full_unstemmed |
In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the trigeminal ganglia |
title_sort |
in vivo dynamics of aav-mediated gene delivery to sensory neurons of the trigeminal ganglia |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-04-01 |
description |
Abstract The ability to genetically manipulate trigeminal ganglion (TG) neurons would be useful in the study of the craniofacial nervous system and latent alphaherpesvirus infections. We investigated adeno-associated virus (AAV) vectors for gene delivery to the TG after intradermal whiskerpad delivery in mice. We demonstrated that AAV vectors of serotypes 1, 7, 8, and 9 trafficked from the whiskerpad into TG neurons and expressed transgenes within cell bodies and axons of sensory neurons in all three branches of the TG. Gene expression was highest with AAV1, and steadily increased over time up to day 28. Both constitutive and neuronal-specific promoters were able to drive transgene expression in TG neurons. Levels of vector genomes in the TG increased with input dose, and multiple transgenes could be co-delivered to TG neurons by separate AAV vectors. In conclusion, AAV1 vectors are suitable for gene delivery to TG sensory neurons following intradermal whiskerpad injection. |
url |
https://doi.org/10.1038/s41598-017-01004-y |
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