| Comparison of AAV serotypes for gene delivery to dorsal root ganglion neurons. | |
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MedLine Citation:
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PMID: 20179682 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Matthew R J Mason; Erich M E Ehlert; Ruben Eggers; Chris W Pool; Stephan Hermening; Angelina Huseinovic; Eric Timmermans; Bas Blits; Joost Verhaagen |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-23 |
Journal Detail:
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Title: Molecular therapy : the journal of the American Society of Gene Therapy Volume: 18 ISSN: 1525-0024 ISO Abbreviation: Mol. Ther. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-01 Completed Date: 2010-07-08 Revised Date: 2011-07-27 |
Medline Journal Info:
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Nlm Unique ID: 100890581 Medline TA: Mol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 715-24 Citation Subset: IM |
Affiliation:
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Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Institute of the Royal Academy of Arts and Sciences, Amsterdam, the Netherlands. m.mason@nin.knaw.nl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Dependovirus / classification*, genetics Female Ganglia, Spinal* Gene Therapy* Genetic Vectors* Plasmids Rats Rats, Wistar Serotyping Transduction, Genetic |
| Comments/Corrections | |
Comment In:
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Mol Ther. 2010 Apr;18(4):670-3
[PMID:
20357781
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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