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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Main Authors: Chung H. Dang, Martine Aubert, Harshana S. De Silva Feelixge, Kurt Diem, Michelle A. Loprieno, Pavitra Roychoudhury, Daniel Stone, Keith R. Jerome
Format: Article
Language:English
Published: Nature Publishing Group 2017-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-01004-y
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spelling 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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