Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption

Autores
Orlowski, Alejandro; Katz, Michael G.; Gubara, Sarah M.; Fargnoli, Anthony S.; Fish, Kenneth M.; Weber, Thomas
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Gene therapy with adeno-associated virus (AAV)-based vectors shows great promise for the gene therapeutic treatment of a broad array of diseases. In fact, the treatment of genetic diseases with AAV vectors is currently the only in vivo gene therapy approach that is approved by the US Food and Drug Administration (FDA). Unfortunately, pre-existing antibodies against AAV severely limit the patient population that can potentially benefit from AAV gene therapy, especially if the vector is delivered by intravenous injection. Here, we demonstrate that we can selectively deplete antiAAV antibodies by hemapheresis combined with AAV9 particles coupled to Sepharose beads. In rats that underwent hemapheresis and immunoadsorption, luciferase expression was dramatically increased in the hearts and fully restored in the livers of these rats. Importantly, our method can be readily adapted for the use in clinical AAV gene therapy.
Fil: Orlowski, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados Unidos
Fil: Katz, Michael G.. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados Unidos
Fil: Gubara, Sarah M.. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados Unidos
Fil: Fargnoli, Anthony S.. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados Unidos
Fil: Fish, Kenneth M.. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados Unidos
Fil: Weber, Thomas. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados Unidos
Materia
AAV
Neutralizing Antibodies
Gene Therapy
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/142967
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorptionOrlowski, AlejandroKatz, Michael G.Gubara, Sarah M.Fargnoli, Anthony S.Fish, Kenneth M.Weber, ThomasAAVNeutralizing AntibodiesGene Therapyhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Gene therapy with adeno-associated virus (AAV)-based vectors shows great promise for the gene therapeutic treatment of a broad array of diseases. In fact, the treatment of genetic diseases with AAV vectors is currently the only in vivo gene therapy approach that is approved by the US Food and Drug Administration (FDA). Unfortunately, pre-existing antibodies against AAV severely limit the patient population that can potentially benefit from AAV gene therapy, especially if the vector is delivered by intravenous injection. Here, we demonstrate that we can selectively deplete antiAAV antibodies by hemapheresis combined with AAV9 particles coupled to Sepharose beads. In rats that underwent hemapheresis and immunoadsorption, luciferase expression was dramatically increased in the hearts and fully restored in the livers of these rats. Importantly, our method can be readily adapted for the use in clinical AAV gene therapy.Fil: Orlowski, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados UnidosFil: Katz, Michael G.. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados UnidosFil: Gubara, Sarah M.. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados UnidosFil: Fargnoli, Anthony S.. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados UnidosFil: Fish, Kenneth M.. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados UnidosFil: Weber, Thomas. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados UnidosCell Press2020-03-13info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/142967Orlowski, Alejandro; Katz, Michael G.; Gubara, Sarah M.; Fargnoli, Anthony S.; Fish, Kenneth M.; et al.; Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption; Cell Press; Molecular Therapy - Methods and Clinical Development; 16; 13-3-2020; 192-2032329-0501CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2329050120300152info:eu-repo/semantics/altIdentifier/doi/10.1016/j.omtm.2020.01.004info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:24:51Zoai:ri.conicet.gov.ar:11336/142967instacron: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 10:24:51.489CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption
title Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption
spellingShingle Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption
Orlowski, Alejandro
AAV
Neutralizing Antibodies
Gene Therapy
title_short Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption
title_full Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption
title_fullStr Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption
title_full_unstemmed Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption
title_sort Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption
dc.creator.none.fl_str_mv Orlowski, Alejandro
Katz, Michael G.
Gubara, Sarah M.
Fargnoli, Anthony S.
Fish, Kenneth M.
Weber, Thomas
author Orlowski, Alejandro
author_facet Orlowski, Alejandro
Katz, Michael G.
Gubara, Sarah M.
Fargnoli, Anthony S.
Fish, Kenneth M.
Weber, Thomas
author_role author
author2 Katz, Michael G.
Gubara, Sarah M.
Fargnoli, Anthony S.
Fish, Kenneth M.
Weber, Thomas
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv AAV
Neutralizing Antibodies
Gene Therapy
topic AAV
Neutralizing Antibodies
Gene Therapy
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Gene therapy with adeno-associated virus (AAV)-based vectors shows great promise for the gene therapeutic treatment of a broad array of diseases. In fact, the treatment of genetic diseases with AAV vectors is currently the only in vivo gene therapy approach that is approved by the US Food and Drug Administration (FDA). Unfortunately, pre-existing antibodies against AAV severely limit the patient population that can potentially benefit from AAV gene therapy, especially if the vector is delivered by intravenous injection. Here, we demonstrate that we can selectively deplete antiAAV antibodies by hemapheresis combined with AAV9 particles coupled to Sepharose beads. In rats that underwent hemapheresis and immunoadsorption, luciferase expression was dramatically increased in the hearts and fully restored in the livers of these rats. Importantly, our method can be readily adapted for the use in clinical AAV gene therapy.
Fil: Orlowski, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados Unidos
Fil: Katz, Michael G.. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados Unidos
Fil: Gubara, Sarah M.. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados Unidos
Fil: Fargnoli, Anthony S.. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados Unidos
Fil: Fish, Kenneth M.. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados Unidos
Fil: Weber, Thomas. Icahn School of Medicine at Mount Sinai. Graduate School of Biomedical Sciences. Cardiovascular Institute; Estados Unidos
description Gene therapy with adeno-associated virus (AAV)-based vectors shows great promise for the gene therapeutic treatment of a broad array of diseases. In fact, the treatment of genetic diseases with AAV vectors is currently the only in vivo gene therapy approach that is approved by the US Food and Drug Administration (FDA). Unfortunately, pre-existing antibodies against AAV severely limit the patient population that can potentially benefit from AAV gene therapy, especially if the vector is delivered by intravenous injection. Here, we demonstrate that we can selectively deplete antiAAV antibodies by hemapheresis combined with AAV9 particles coupled to Sepharose beads. In rats that underwent hemapheresis and immunoadsorption, luciferase expression was dramatically increased in the hearts and fully restored in the livers of these rats. Importantly, our method can be readily adapted for the use in clinical AAV gene therapy.
publishDate 2020
dc.date.none.fl_str_mv 2020-03-13
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/11336/142967
Orlowski, Alejandro; Katz, Michael G.; Gubara, Sarah M.; Fargnoli, Anthony S.; Fish, Kenneth M.; et al.; Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption; Cell Press; Molecular Therapy - Methods and Clinical Development; 16; 13-3-2020; 192-203
2329-0501
CONICET Digital
CONICET
url http://hdl.handle.net/11336/142967
identifier_str_mv Orlowski, Alejandro; Katz, Michael G.; Gubara, Sarah M.; Fargnoli, Anthony S.; Fish, Kenneth M.; et al.; Successful transduction with AAV vectors after selective depletion of anti-AAV antibodies by immunoadsorption; Cell Press; Molecular Therapy - Methods and Clinical Development; 16; 13-3-2020; 192-203
2329-0501
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2329050120300152
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.omtm.2020.01.004
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
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
_version_ 1844614246152798208
score 13.070432

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