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Comparison of AAV Serotypes for Gene Delivery to Dorsal Root Ganglion Neurons
- 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.
- Subjects :
- Transgene
Genetic Vectors
Sensory system
Calcitonin gene-related peptide
Gene delivery
Biology
Green fluorescent protein
Mice
Transduction (genetics)
Dorsal root ganglion
Transduction, Genetic
Ganglia, Spinal
Commentaries
Drug Discovery
Genetics
medicine
Humans
Animals
Rats, Wistar
Serotyping
Molecular Biology
Pharmacology
Peripheral Nervous System Diseases
Original Articles
Genetic Therapy
Dependovirus
Molecular biology
Rats
medicine.anatomical_structure
nervous system
Peripheral nervous system
Molecular Medicine
Female
Reassortant Viruses
Plasmids
Subjects
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