Tissue damage modeling in gene electrotransfer: the role of pH

Autores
Olaiz, Nahuel Manuel; Signori, Emanuela; Maglietti, Felipe Horacio; Soba, Alejandro; Suárez, Cecilia Ana; Turjanski, Pablo Guillermo; Michinski, Sebastián Diego; Marshall, Guillermo Ricardo
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Optimal gene electrotransfer (GET) requires a compromise between maximum transgene expression and minimal tissue damage. GET in skeletal muscle can be improved by pretreatment with hyaluronidase which contributes to maximize transgene uptake and expression. Nevertheless, tissue damage remains severe close to the electrodes, with a concomitant loss of GET efficiency. Here we analyze the role of pH in tissue damage in GET protocols through in vivo modeling using a transparent chamber implanted into the dorsal skinfold of a mouse (DSC) and intravital microscopy, and in silico modeling using the Poisson–Nernst–Planck equations for ion transport. DSC intravital microscopy reveals the existence of pH fronts emerging from both electrodes and that these fronts are immediate and substantial thus giving rise to tissue necrosis. Theoretical modeling confirms experimental measurements and shows that in GET protocols whether with or without hyaluronidase pretreatment, pH fronts are the principal cause of muscle damage near the electrodes. It also predicts that an optimal efficiency in GET protocols, that is a compromise between obtaining maximum electroporated area and minimal tissue damage, is achieved when the electric field applied is near 183 V/cm in a GET protocol and 158 V/cm in a hyaluronidase + GET protocol.
Fil: Olaiz, Nahuel Manuel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Signori, Emanuela. Istituto di Farmacologia Traslazionale; Italia
Fil: Maglietti, Felipe Horacio. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Soba, Alejandro. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Suárez, Cecilia Ana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Turjanski, Pablo Guillermo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Michinski, Sebastián Diego. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Marshall, Guillermo Ricardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Gene Electrotransfer
Ph
Hyaluronidase
Computational Modeling
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/19317
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/19317
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Tissue damage modeling in gene electrotransfer: the role of pHOlaiz, Nahuel ManuelSignori, EmanuelaMaglietti, Felipe HoracioSoba, AlejandroSuárez, Cecilia AnaTurjanski, Pablo GuillermoMichinski, Sebastián DiegoMarshall, Guillermo RicardoGene ElectrotransferPhHyaluronidaseComputational Modelinghttps://purl.org/becyt/ford/1.2https://purl.org/becyt/ford/1Optimal gene electrotransfer (GET) requires a compromise between maximum transgene expression and minimal tissue damage. GET in skeletal muscle can be improved by pretreatment with hyaluronidase which contributes to maximize transgene uptake and expression. Nevertheless, tissue damage remains severe close to the electrodes, with a concomitant loss of GET efficiency. Here we analyze the role of pH in tissue damage in GET protocols through in vivo modeling using a transparent chamber implanted into the dorsal skinfold of a mouse (DSC) and intravital microscopy, and in silico modeling using the Poisson–Nernst–Planck equations for ion transport. DSC intravital microscopy reveals the existence of pH fronts emerging from both electrodes and that these fronts are immediate and substantial thus giving rise to tissue necrosis. Theoretical modeling confirms experimental measurements and shows that in GET protocols whether with or without hyaluronidase pretreatment, pH fronts are the principal cause of muscle damage near the electrodes. It also predicts that an optimal efficiency in GET protocols, that is a compromise between obtaining maximum electroporated area and minimal tissue damage, is achieved when the electric field applied is near 183 V/cm in a GET protocol and 158 V/cm in a hyaluronidase + GET protocol.Fil: Olaiz, Nahuel Manuel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Signori, Emanuela. Istituto di Farmacologia Traslazionale; ItaliaFil: Maglietti, Felipe Horacio. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Soba, Alejandro. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Suárez, Cecilia Ana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Turjanski, Pablo Guillermo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Michinski, Sebastián Diego. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marshall, Guillermo Ricardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Science2014-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/19317Olaiz, Nahuel Manuel; Signori, Emanuela; Maglietti, Felipe Horacio; Soba, Alejandro; Suárez, Cecilia Ana; et al.; Tissue damage modeling in gene electrotransfer: the role of pH; Elsevier Science; Bioelectrochemistry; 100; 12-2014; 105-1111567-5394CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bioelechem.2014.05.001info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1567539414000784info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:30Zoai:ri.conicet.gov.ar:11336/19317instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:59:31.238CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tissue damage modeling in gene electrotransfer: the role of pH
title Tissue damage modeling in gene electrotransfer: the role of pH
spellingShingle Tissue damage modeling in gene electrotransfer: the role of pH
Olaiz, Nahuel Manuel
Gene Electrotransfer
Ph
Hyaluronidase
Computational Modeling
title_short Tissue damage modeling in gene electrotransfer: the role of pH
title_full Tissue damage modeling in gene electrotransfer: the role of pH
title_fullStr Tissue damage modeling in gene electrotransfer: the role of pH
title_full_unstemmed Tissue damage modeling in gene electrotransfer: the role of pH
title_sort Tissue damage modeling in gene electrotransfer: the role of pH
dc.creator.none.fl_str_mv Olaiz, Nahuel Manuel
Signori, Emanuela
Maglietti, Felipe Horacio
Soba, Alejandro
Suárez, Cecilia Ana
Turjanski, Pablo Guillermo
Michinski, Sebastián Diego
Marshall, Guillermo Ricardo
author Olaiz, Nahuel Manuel
author_facet Olaiz, Nahuel Manuel
Signori, Emanuela
Maglietti, Felipe Horacio
Soba, Alejandro
Suárez, Cecilia Ana
Turjanski, Pablo Guillermo
Michinski, Sebastián Diego
Marshall, Guillermo Ricardo
author_role author
author2 Signori, Emanuela
Maglietti, Felipe Horacio
Soba, Alejandro
Suárez, Cecilia Ana
Turjanski, Pablo Guillermo
Michinski, Sebastián Diego
Marshall, Guillermo Ricardo
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Gene Electrotransfer
Ph
Hyaluronidase
Computational Modeling
topic Gene Electrotransfer
Ph
Hyaluronidase
Computational Modeling
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.2
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Optimal gene electrotransfer (GET) requires a compromise between maximum transgene expression and minimal tissue damage. GET in skeletal muscle can be improved by pretreatment with hyaluronidase which contributes to maximize transgene uptake and expression. Nevertheless, tissue damage remains severe close to the electrodes, with a concomitant loss of GET efficiency. Here we analyze the role of pH in tissue damage in GET protocols through in vivo modeling using a transparent chamber implanted into the dorsal skinfold of a mouse (DSC) and intravital microscopy, and in silico modeling using the Poisson–Nernst–Planck equations for ion transport. DSC intravital microscopy reveals the existence of pH fronts emerging from both electrodes and that these fronts are immediate and substantial thus giving rise to tissue necrosis. Theoretical modeling confirms experimental measurements and shows that in GET protocols whether with or without hyaluronidase pretreatment, pH fronts are the principal cause of muscle damage near the electrodes. It also predicts that an optimal efficiency in GET protocols, that is a compromise between obtaining maximum electroporated area and minimal tissue damage, is achieved when the electric field applied is near 183 V/cm in a GET protocol and 158 V/cm in a hyaluronidase + GET protocol.
Fil: Olaiz, Nahuel Manuel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Signori, Emanuela. Istituto di Farmacologia Traslazionale; Italia
Fil: Maglietti, Felipe Horacio. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Soba, Alejandro. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Suárez, Cecilia Ana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Turjanski, Pablo Guillermo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Michinski, Sebastián Diego. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Marshall, Guillermo Ricardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Optimal gene electrotransfer (GET) requires a compromise between maximum transgene expression and minimal tissue damage. GET in skeletal muscle can be improved by pretreatment with hyaluronidase which contributes to maximize transgene uptake and expression. Nevertheless, tissue damage remains severe close to the electrodes, with a concomitant loss of GET efficiency. Here we analyze the role of pH in tissue damage in GET protocols through in vivo modeling using a transparent chamber implanted into the dorsal skinfold of a mouse (DSC) and intravital microscopy, and in silico modeling using the Poisson–Nernst–Planck equations for ion transport. DSC intravital microscopy reveals the existence of pH fronts emerging from both electrodes and that these fronts are immediate and substantial thus giving rise to tissue necrosis. Theoretical modeling confirms experimental measurements and shows that in GET protocols whether with or without hyaluronidase pretreatment, pH fronts are the principal cause of muscle damage near the electrodes. It also predicts that an optimal efficiency in GET protocols, that is a compromise between obtaining maximum electroporated area and minimal tissue damage, is achieved when the electric field applied is near 183 V/cm in a GET protocol and 158 V/cm in a hyaluronidase + GET protocol.
publishDate 2014
dc.date.none.fl_str_mv 2014-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/19317
Olaiz, Nahuel Manuel; Signori, Emanuela; Maglietti, Felipe Horacio; Soba, Alejandro; Suárez, Cecilia Ana; et al.; Tissue damage modeling in gene electrotransfer: the role of pH; Elsevier Science; Bioelectrochemistry; 100; 12-2014; 105-111
1567-5394
CONICET Digital
CONICET
url http://hdl.handle.net/11336/19317
identifier_str_mv Olaiz, Nahuel Manuel; Signori, Emanuela; Maglietti, Felipe Horacio; Soba, Alejandro; Suárez, Cecilia Ana; et al.; Tissue damage modeling in gene electrotransfer: the role of pH; Elsevier Science; Bioelectrochemistry; 100; 12-2014; 105-111
1567-5394
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bioelechem.2014.05.001
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1567539414000784
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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