title: Comparison of AAV serotypes for gene delivery to dorsal root ganglion neurons.
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.
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Institute of the Royal Academy of Arts and Sciences, Amsterdam, the Netherlands. m.mason@nin.knaw.nl
authors.forename: Matthew R J
authors.initials: MR
authors.lastname: Mason
authors.forename: Erich M E
authors.initials: EM
authors.lastname: Ehlert
authors.forename: Ruben
authors.initials: R
authors.lastname: Eggers
authors.forename: Chris W
authors.initials: CW
authors.lastname: Pool
authors.forename: Stephan
authors.initials: S
authors.lastname: Hermening
authors.forename: Angelina
authors.initials: A
authors.lastname: Huseinovic
authors.forename: Eric
authors.initials: E
authors.lastname: Timmermans
authors.forename: Bas
authors.initials: B
authors.lastname: Blits
authors.forename: Joost
authors.initials: J
authors.lastname: Verhaagen
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000145:classification* / Q000235:genetics; D005260:Female; D005727:Ganglia, Spinal; D015316:Genetic Therapy; D005822:Genetic Vectors; D010957:Plasmids; D051381:Rats; D017208:Rats, Wistar; D012703:Serotyping; D014161:Transduction, Genetic