Development and assessment of herpes simplex virus type 1 (HSV-1) amplicon vectors with sensory neuron-selective promoters
Entity
UAM. Departamento de Biología MolecularPublisher
MDPIDate
2022-07-30Citation
10.3390/ijms23158474
International Journal of Molecular Sciences 23.15 (2022): 8474
ISSN
1661-6596 (print); 1422-0067 (online)DOI
10.3390/ijms23158474Editor's Version
https://doi.org/10.3390/ijms23158474Subjects
Human Alphaherpesvirus 1; Nerve Cell Plasticity; Neurite Outgrowth; Parasympathetic Ganglion; Sensory Nerve Cell; Spinal Cord Lesion; Biología y Biomedicina / BiologíaRights
© 2022 by the authorsAbstract
Background: Neurogenic detrusor overactivity (NDO) is a severe pathological condition characterized by involuntary detrusor contractions leading to urine leakage. This condition is frequent after spinal cord injury (SCI). Gene therapy for NDO requires the development of vectors that express therapeutic transgenes driven by sensory neuron-specific promoters. The aim of this study was to develop and assess tools for the characterization of sensory neuron-specific promoters in dorsal root ganglia (DRG) neurons after transduction with herpes simplex virus type 1 (HSV-1)-based amplicon defective vectors. Methods: The HSV-1 vector genome encoded two independent transcription cassettes: one expressed firefly luciferase (FLuc) driven by different promoters’ candidates (rTRPV1, rASIC3, rCGRP, or hCGRP), and the other expressed a reporter gene driven by an invariable promoter. The strength and selectivity of promoters was assessed in organotypic cultures of explanted adult DRG, or sympathetic and parasympathetic ganglia from control and SCI rats. Results: The rCGRP promoter induced selective expression in the DRG of normal rats. The rTRPV-1 promoter, which did not display selective activity in control rats, induced selective expression in DRG explanted from SCI rats. Conclusions: This study provides a methodology to assess sensory neuron-specific promoters, opening new perspectives for future gene therapy for NDO
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Google Scholar:Joussain, Charles
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Le Coz, Olivier
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Pichugin, Andrey
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Marconi, Peggy
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Lim, Filip
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Sicurella, Mariaconcetta
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Foster, Keith
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Giuliano, François
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Epstein, Alberto L.
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Aranda Muñoz, Alejandro
This item appears in the following Collection(s)
- Producción científica de la UAM [20700]
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