Specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intra-nerve injection of AAV 6 vector
Adeno-associated virus 6 (AAV6) has been proposed as a potential vector candidate for specific gene expression in pain-related dorsal root ganglion (DRG) neurons, but this has not been confirmed in nonhuman primates. The aim of our study was to analyze the transduction efficiency and target specific...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050121001261 |
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| author | Moeko Kudo Sidikejiang Wupuer Maki Fujiwara Yuko Saito Shinji Kubota Ken-ichi Inoue Masahiko Takada Kazuhiko Seki |
| author_facet | Moeko Kudo Sidikejiang Wupuer Maki Fujiwara Yuko Saito Shinji Kubota Ken-ichi Inoue Masahiko Takada Kazuhiko Seki |
| author_sort | Moeko Kudo |
| collection | DOAJ |
| description | Adeno-associated virus 6 (AAV6) has been proposed as a potential vector candidate for specific gene expression in pain-related dorsal root ganglion (DRG) neurons, but this has not been confirmed in nonhuman primates. The aim of our study was to analyze the transduction efficiency and target specificity of this viral vector in the common marmoset by comparing it with those in the rat. When green fluorescent protein-expressing serotype-6 vector was injected into the sciatic nerve, the efficiency of gene expression in DRG neurons was comparable in both species. We found that the serotype-6 vector was largely specific to the pain-related ganglion neurons in the marmoset, as well as in the rat, whereas the serotype-9 vector resulted in contrasting effects in the two species. Neither AAV6 nor AAV9 resulted in DRG toxicity when administered via the sciatic nerve, suggesting this as a safer route of sensory nerve transduction than the currently used intrathecal or intravenous administrative routes. Furthermore, the AAV6 vector could be an optimal serotype for gene therapy for human chronic pain that has a minimal effect on other somatosensory functions of DRG neurons. |
| first_indexed | 2024-12-14T08:11:50Z |
| format | Article |
| id | doaj.art-15848c6c69374436be4b3606c43fb0b6 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-14T08:11:50Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-15848c6c69374436be4b3606c43fb0b62022-12-21T23:10:03ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012021-12-01231122Specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intra-nerve injection of AAV 6 vectorMoeko Kudo0Sidikejiang Wupuer1Maki Fujiwara2Yuko Saito3Shinji Kubota4Ken-ichi Inoue5Masahiko Takada6Kazuhiko Seki7Department of Neurophysiology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, JapanDepartment of Neurophysiology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, JapanSystems Neuroscience Section, Department of Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Aichi, JapanDepartment of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, JapanDepartment of Neurophysiology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, JapanSystems Neuroscience Section, Department of Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Aichi, JapanSystems Neuroscience Section, Department of Neuroscience, Primate Research Institute, Kyoto University, Inuyama, Aichi, JapanDepartment of Neurophysiology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan; Corresponding author: Kazuhiko Seki, Department of Neurophysiology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.Adeno-associated virus 6 (AAV6) has been proposed as a potential vector candidate for specific gene expression in pain-related dorsal root ganglion (DRG) neurons, but this has not been confirmed in nonhuman primates. The aim of our study was to analyze the transduction efficiency and target specificity of this viral vector in the common marmoset by comparing it with those in the rat. When green fluorescent protein-expressing serotype-6 vector was injected into the sciatic nerve, the efficiency of gene expression in DRG neurons was comparable in both species. We found that the serotype-6 vector was largely specific to the pain-related ganglion neurons in the marmoset, as well as in the rat, whereas the serotype-9 vector resulted in contrasting effects in the two species. Neither AAV6 nor AAV9 resulted in DRG toxicity when administered via the sciatic nerve, suggesting this as a safer route of sensory nerve transduction than the currently used intrathecal or intravenous administrative routes. Furthermore, the AAV6 vector could be an optimal serotype for gene therapy for human chronic pain that has a minimal effect on other somatosensory functions of DRG neurons.http://www.sciencedirect.com/science/article/pii/S2329050121001261marmosetratAAV6AAV9DRG afferentssomatosensory |
| spellingShingle | Moeko Kudo Sidikejiang Wupuer Maki Fujiwara Yuko Saito Shinji Kubota Ken-ichi Inoue Masahiko Takada Kazuhiko Seki Specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intra-nerve injection of AAV 6 vector Molecular Therapy: Methods & Clinical Development marmoset rat AAV6 AAV9 DRG afferents somatosensory |
| title | Specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intra-nerve injection of AAV 6 vector |
| title_full | Specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intra-nerve injection of AAV 6 vector |
| title_fullStr | Specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intra-nerve injection of AAV 6 vector |
| title_full_unstemmed | Specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intra-nerve injection of AAV 6 vector |
| title_short | Specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intra-nerve injection of AAV 6 vector |
| title_sort | specific gene expression in unmyelinated dorsal root ganglion neurons in nonhuman primates by intra nerve injection of aav 6 vector |
| topic | marmoset rat AAV6 AAV9 DRG afferents somatosensory |
| url | http://www.sciencedirect.com/science/article/pii/S2329050121001261 |
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