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Development and Assessment of Herpes Simplex Virus Type 1 (HSV-1) Amplicon Vectors with Sensory Neuron-Selective Promoters

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 therapeu...

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Autores principales: Joussain, Charles, Le Coz, Olivier, Pichugin, Andrey, Marconi, Peggy, Lim, Filip, Sicurella, Mariaconcetta, Foster, Keith, Giuliano, François, Epstein, Alberto L., Aranda Muñoz, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369297/
https://www.ncbi.nlm.nih.gov/pubmed/35955608
http://dx.doi.org/10.3390/ijms23158474
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author Joussain, Charles
Le Coz, Olivier
Pichugin, Andrey
Marconi, Peggy
Lim, Filip
Sicurella, Mariaconcetta
Foster, Keith
Giuliano, François
Epstein, Alberto L.
Aranda Muñoz, Alejandro
author_facet Joussain, Charles
Le Coz, Olivier
Pichugin, Andrey
Marconi, Peggy
Lim, Filip
Sicurella, Mariaconcetta
Foster, Keith
Giuliano, François
Epstein, Alberto L.
Aranda Muñoz, Alejandro
author_sort Joussain, Charles
collection PubMed
description 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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spelling pubmed-93692972022-08-12 Development and Assessment of Herpes Simplex Virus Type 1 (HSV-1) Amplicon Vectors with Sensory Neuron-Selective Promoters Joussain, Charles Le Coz, Olivier Pichugin, Andrey Marconi, Peggy Lim, Filip Sicurella, Mariaconcetta Foster, Keith Giuliano, François Epstein, Alberto L. Aranda Muñoz, Alejandro Int J Mol Sci Article 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. MDPI 2022-07-30 /pmc/articles/PMC9369297/ /pubmed/35955608 http://dx.doi.org/10.3390/ijms23158474 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Joussain, Charles
Le Coz, Olivier
Pichugin, Andrey
Marconi, Peggy
Lim, Filip
Sicurella, Mariaconcetta
Foster, Keith
Giuliano, François
Epstein, Alberto L.
Aranda Muñoz, Alejandro
Development and Assessment of Herpes Simplex Virus Type 1 (HSV-1) Amplicon Vectors with Sensory Neuron-Selective Promoters
title Development and Assessment of Herpes Simplex Virus Type 1 (HSV-1) Amplicon Vectors with Sensory Neuron-Selective Promoters
title_full Development and Assessment of Herpes Simplex Virus Type 1 (HSV-1) Amplicon Vectors with Sensory Neuron-Selective Promoters
title_fullStr Development and Assessment of Herpes Simplex Virus Type 1 (HSV-1) Amplicon Vectors with Sensory Neuron-Selective Promoters
title_full_unstemmed Development and Assessment of Herpes Simplex Virus Type 1 (HSV-1) Amplicon Vectors with Sensory Neuron-Selective Promoters
title_short Development and Assessment of Herpes Simplex Virus Type 1 (HSV-1) Amplicon Vectors with Sensory Neuron-Selective Promoters
title_sort development and assessment of herpes simplex virus type 1 (hsv-1) amplicon vectors with sensory neuron-selective promoters
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369297/
https://www.ncbi.nlm.nih.gov/pubmed/35955608
http://dx.doi.org/10.3390/ijms23158474
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