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Comparison of AAV Serotypes for Gene Delivery to Dorsal Root Ganglion Neurons

Authors :
Chris W. Pool
Erich M. E. Ehlert
Ruben Eggers
Stephan Hermening
Bas Blits
Joost Verhaagen
Angelina Huseinovic
Eric Jacobus Hubertus Timmermans
Matthew R. J. Mason
Netherlands Institute for Neuroscience (NIN)
Source :
Molecular Therapy, 18, 715-724. Nature Publishing Group
Publication Year :
2010
Publisher :
Elsevier BV, 2010.

Abstract

For many experiments in the study of the peripheral nervous system, it would be useful to genetically manipulate primary sensory neurons. We have compared vectors based on adeno-associated virus (AAV) serotypes 1, 2, 3, 4, 5, 6, and 8, and lentivirus (LV), all expressing green fluorescent protein (GFP), for efficiency of transduction of sensory neurons, expression level, cellular tropism, and persistence of transgene expression following direct injection into the dorsal root ganglia (DRG), using histological quantification and qPCR. Two weeks after injection, AAV1, AAV5, and AAV6 had transduced the most neurons. The time course of GFP expression from these three vectors was studied from 1 to 12 weeks after injection. AAV5 was the most effective serotype overall, followed by AAV1. Both these serotypes showed increasing neuronal transduction rates at later time points, with some injections of AAV5 yielding over 90% of DRG neurons GFP(+) at 12 weeks. AAV6 performed well initially, but transduction rates declined dramatically between 4 and 12 weeks. AAV1 and AAV5 both transduced large-diameter neurons, IB4(+) neurons, and CGRP(+) neurons. In conclusion, AAV5 is a highly effective gene therapy vector for primary sensory neurons following direct injection into the DRG.

Details

ISSN :
15250016
Volume :
18
Database :
OpenAIRE
Journal :
Molecular Therapy
Accession number :
edsair.doi.dedup.....86e2380332e52c9871a4df8924f83020
Full Text :
https://doi.org/10.1038/mt.2010.19