Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs

Autores
Girard Gagnepain, Anais; Amirache, Fouzia; Costa, Caroline; Lévy, Camille; Frecha, Cecilia Ariana; Fusil, Floriane; Nègre, Didier; Lavillette, Dimitri; Cosset, François-Loïc; Verhoeyen, Els
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Hematopoietic stem cell (HSC)-based gene therapy holds promise for the cure of many diseases. The field is now moving toward the use of lentiviral vectors (LVs) as evidenced by 4 successful clinical trials. These trials used vesicular-stomatitis-virus-G protein (VSV-G)-LVs at high doses combined with strong cytokine-cocktail stimulation to obtain therapeutically relevant transduction levels; however, they might compromise the HSC character. Summarizing all these disadvantages, alternatives to VSV-G-LVs are urgently needed. We generated here high-titer LVs pseudotyped with a baboon retroviral envelope glycoprotein (BaEV-LVs), resistant to human complement. Under mild cytokine prestimulation to preserve the HSC characteristics, a single BaEV-LV application at a low dose, resulted in up to 90% of hCD34+ cell transduction. Even more striking was that these new BaEV-LVs allowed, at low doses, efficient transduction of up to 30% of quiescent hCD34+ cells, whereas high-dose VSV-G-LVs were insufficient. Importantly, reconstitution of NOD/Lt-SCID/γc−/− (NSG) mice with BaEV-LV-transduced hCD34+ cells maintained these high transduction levels in all myeloid and lymphoid lineages, including early progenitors. This transduction pattern was confirmed or even increased in secondary NSG recipient mice. This suggests that BaEV-LVs efficiently transduce true HSCs and could improve HSC-based gene therapy, for which high-level HSC correction is needed for life-long cure.
Fil: Girard Gagnepain, Anais. Université Claude Bernard Lyon 1; Francia
Fil: Amirache, Fouzia. Université Claude Bernard Lyon 1; Francia
Fil: Costa, Caroline. Université Claude Bernard Lyon 1; Francia
Fil: Lévy, Camille. Université Claude Bernard Lyon 1; Francia
Fil: Frecha, Cecilia Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina
Fil: Fusil, Floriane. Université Claude Bernard Lyon 1; Francia
Fil: Nègre, Didier. Université Claude Bernard Lyon 1; Francia
Fil: Lavillette, Dimitri. Centre National de la Recherche Scientifique; Francia
Fil: Cosset, François-Loïc. Université Claude Bernard Lyon 1; Francia
Fil: Verhoeyen, Els. Université Claude Bernard Lyon 1; Francia. Inserm; Francia
Materia
Hematopoietic Stem Cells Gene Therapy
Baboon Envelope
Lentiviral Vectors
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:11336/17590
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/17590
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCsGirard Gagnepain, AnaisAmirache, FouziaCosta, CarolineLévy, CamilleFrecha, Cecilia ArianaFusil, FlorianeNègre, DidierLavillette, DimitriCosset, François-LoïcVerhoeyen, ElsHematopoietic Stem Cells Gene TherapyBaboon EnvelopeLentiviral Vectorshttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Hematopoietic stem cell (HSC)-based gene therapy holds promise for the cure of many diseases. The field is now moving toward the use of lentiviral vectors (LVs) as evidenced by 4 successful clinical trials. These trials used vesicular-stomatitis-virus-G protein (VSV-G)-LVs at high doses combined with strong cytokine-cocktail stimulation to obtain therapeutically relevant transduction levels; however, they might compromise the HSC character. Summarizing all these disadvantages, alternatives to VSV-G-LVs are urgently needed. We generated here high-titer LVs pseudotyped with a baboon retroviral envelope glycoprotein (BaEV-LVs), resistant to human complement. Under mild cytokine prestimulation to preserve the HSC characteristics, a single BaEV-LV application at a low dose, resulted in up to 90% of hCD34+ cell transduction. Even more striking was that these new BaEV-LVs allowed, at low doses, efficient transduction of up to 30% of quiescent hCD34+ cells, whereas high-dose VSV-G-LVs were insufficient. Importantly, reconstitution of NOD/Lt-SCID/γc−/− (NSG) mice with BaEV-LV-transduced hCD34+ cells maintained these high transduction levels in all myeloid and lymphoid lineages, including early progenitors. This transduction pattern was confirmed or even increased in secondary NSG recipient mice. This suggests that BaEV-LVs efficiently transduce true HSCs and could improve HSC-based gene therapy, for which high-level HSC correction is needed for life-long cure.Fil: Girard Gagnepain, Anais. Université Claude Bernard Lyon 1; FranciaFil: Amirache, Fouzia. Université Claude Bernard Lyon 1; FranciaFil: Costa, Caroline. Université Claude Bernard Lyon 1; FranciaFil: Lévy, Camille. Université Claude Bernard Lyon 1; FranciaFil: Frecha, Cecilia Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; ArgentinaFil: Fusil, Floriane. Université Claude Bernard Lyon 1; FranciaFil: Nègre, Didier. Université Claude Bernard Lyon 1; FranciaFil: Lavillette, Dimitri. Centre National de la Recherche Scientifique; FranciaFil: Cosset, François-Loïc. Université Claude Bernard Lyon 1; FranciaFil: Verhoeyen, Els. Université Claude Bernard Lyon 1; Francia. Inserm; FranciaAmerican Society of Hematology2014-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/17590Girard Gagnepain, Anais; Amirache, Fouzia; Costa, Caroline; Lévy, Camille; Frecha, Cecilia Ariana; et al.; Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs; American Society of Hematology; Blood, The Journal Of The American Society Of Hematology - Print; 124; 8; 8-2014; 1221-12310006-4971enginfo:eu-repo/semantics/altIdentifier/url/http://www.bloodjournal.org/content/124/8/1221.long?sso-checked=trueinfo:eu-repo/semantics/altIdentifier/doi/10.1182/blood-2014-02-558163info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:36:45Zoai:ri.conicet.gov.ar:11336/17590instacron: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:34982025-09-29 09:36:46.078CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs
title Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs
spellingShingle Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs
Girard Gagnepain, Anais
Hematopoietic Stem Cells Gene Therapy
Baboon Envelope
Lentiviral Vectors
title_short Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs
title_full Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs
title_fullStr Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs
title_full_unstemmed Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs
title_sort Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs
dc.creator.none.fl_str_mv Girard Gagnepain, Anais
Amirache, Fouzia
Costa, Caroline
Lévy, Camille
Frecha, Cecilia Ariana
Fusil, Floriane
Nègre, Didier
Lavillette, Dimitri
Cosset, François-Loïc
Verhoeyen, Els
author Girard Gagnepain, Anais
author_facet Girard Gagnepain, Anais
Amirache, Fouzia
Costa, Caroline
Lévy, Camille
Frecha, Cecilia Ariana
Fusil, Floriane
Nègre, Didier
Lavillette, Dimitri
Cosset, François-Loïc
Verhoeyen, Els
author_role author
author2 Amirache, Fouzia
Costa, Caroline
Lévy, Camille
Frecha, Cecilia Ariana
Fusil, Floriane
Nègre, Didier
Lavillette, Dimitri
Cosset, François-Loïc
Verhoeyen, Els
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hematopoietic Stem Cells Gene Therapy
Baboon Envelope
Lentiviral Vectors
topic Hematopoietic Stem Cells Gene Therapy
Baboon Envelope
Lentiviral Vectors
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hematopoietic stem cell (HSC)-based gene therapy holds promise for the cure of many diseases. The field is now moving toward the use of lentiviral vectors (LVs) as evidenced by 4 successful clinical trials. These trials used vesicular-stomatitis-virus-G protein (VSV-G)-LVs at high doses combined with strong cytokine-cocktail stimulation to obtain therapeutically relevant transduction levels; however, they might compromise the HSC character. Summarizing all these disadvantages, alternatives to VSV-G-LVs are urgently needed. We generated here high-titer LVs pseudotyped with a baboon retroviral envelope glycoprotein (BaEV-LVs), resistant to human complement. Under mild cytokine prestimulation to preserve the HSC characteristics, a single BaEV-LV application at a low dose, resulted in up to 90% of hCD34+ cell transduction. Even more striking was that these new BaEV-LVs allowed, at low doses, efficient transduction of up to 30% of quiescent hCD34+ cells, whereas high-dose VSV-G-LVs were insufficient. Importantly, reconstitution of NOD/Lt-SCID/γc−/− (NSG) mice with BaEV-LV-transduced hCD34+ cells maintained these high transduction levels in all myeloid and lymphoid lineages, including early progenitors. This transduction pattern was confirmed or even increased in secondary NSG recipient mice. This suggests that BaEV-LVs efficiently transduce true HSCs and could improve HSC-based gene therapy, for which high-level HSC correction is needed for life-long cure.
Fil: Girard Gagnepain, Anais. Université Claude Bernard Lyon 1; Francia
Fil: Amirache, Fouzia. Université Claude Bernard Lyon 1; Francia
Fil: Costa, Caroline. Université Claude Bernard Lyon 1; Francia
Fil: Lévy, Camille. Université Claude Bernard Lyon 1; Francia
Fil: Frecha, Cecilia Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina
Fil: Fusil, Floriane. Université Claude Bernard Lyon 1; Francia
Fil: Nègre, Didier. Université Claude Bernard Lyon 1; Francia
Fil: Lavillette, Dimitri. Centre National de la Recherche Scientifique; Francia
Fil: Cosset, François-Loïc. Université Claude Bernard Lyon 1; Francia
Fil: Verhoeyen, Els. Université Claude Bernard Lyon 1; Francia. Inserm; Francia
description Hematopoietic stem cell (HSC)-based gene therapy holds promise for the cure of many diseases. The field is now moving toward the use of lentiviral vectors (LVs) as evidenced by 4 successful clinical trials. These trials used vesicular-stomatitis-virus-G protein (VSV-G)-LVs at high doses combined with strong cytokine-cocktail stimulation to obtain therapeutically relevant transduction levels; however, they might compromise the HSC character. Summarizing all these disadvantages, alternatives to VSV-G-LVs are urgently needed. We generated here high-titer LVs pseudotyped with a baboon retroviral envelope glycoprotein (BaEV-LVs), resistant to human complement. Under mild cytokine prestimulation to preserve the HSC characteristics, a single BaEV-LV application at a low dose, resulted in up to 90% of hCD34+ cell transduction. Even more striking was that these new BaEV-LVs allowed, at low doses, efficient transduction of up to 30% of quiescent hCD34+ cells, whereas high-dose VSV-G-LVs were insufficient. Importantly, reconstitution of NOD/Lt-SCID/γc−/− (NSG) mice with BaEV-LV-transduced hCD34+ cells maintained these high transduction levels in all myeloid and lymphoid lineages, including early progenitors. This transduction pattern was confirmed or even increased in secondary NSG recipient mice. This suggests that BaEV-LVs efficiently transduce true HSCs and could improve HSC-based gene therapy, for which high-level HSC correction is needed for life-long cure.
publishDate 2014
dc.date.none.fl_str_mv 2014-08
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/11336/17590
Girard Gagnepain, Anais; Amirache, Fouzia; Costa, Caroline; Lévy, Camille; Frecha, Cecilia Ariana; et al.; Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs; American Society of Hematology; Blood, The Journal Of The American Society Of Hematology - Print; 124; 8; 8-2014; 1221-1231
0006-4971
url http://hdl.handle.net/11336/17590
identifier_str_mv Girard Gagnepain, Anais; Amirache, Fouzia; Costa, Caroline; Lévy, Camille; Frecha, Cecilia Ariana; et al.; Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs; American Society of Hematology; Blood, The Journal Of The American Society Of Hematology - Print; 124; 8; 8-2014; 1221-1231
0006-4971
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.bloodjournal.org/content/124/8/1221.long?sso-checked=true
info:eu-repo/semantics/altIdentifier/doi/10.1182/blood-2014-02-558163
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
dc.publisher.none.fl_str_mv American Society of Hematology
publisher.none.fl_str_mv American Society of Hematology
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 13.070432

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