STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational Research

STXBP1 syndrome is a severe early-onset epileptic encephalopathy characterized by developmental delay and intellectual disability. This review addresses key challenges in STXBP1 syndrome research, focusing on advanced therapeutic approaches and experimental models. We explore gene therapy strategies...

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Detalhes bibliográficos
Autores: Ruano-Rodríguez, Silvestre, Navarro-Alonso, Mar, Domínguez-Velasco, Benito, Álvarez-Dolado, Manuel, Esteban, Francisco J.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/394847
Acesso em linha:http://hdl.handle.net/10261/394847
https://api.elsevier.com/content/abstract/scopus_id/105001154135
Access Level:acceso abierto
Palavra-chave:STXBP1
Antisense oligonucleotides
Bioinformatics
Epilepsy
Gene and cell therapy
Genomics
Haploinsufficiency
Induced pluripotent stem cells
Infantile epileptic encephalopathy
Murine models
Personalized medicine
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spelling STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational ResearchRuano-Rodríguez, SilvestreNavarro-Alonso, MarDomínguez-Velasco, BenitoÁlvarez-Dolado, ManuelEsteban, Francisco J.STXBP1Antisense oligonucleotidesBioinformaticsEpilepsyGene and cell therapyGenomicsHaploinsufficiencyInduced pluripotent stem cellsInfantile epileptic encephalopathyMurine modelsPersonalized medicineSTXBP1 syndrome is a severe early-onset epileptic encephalopathy characterized by developmental delay and intellectual disability. This review addresses key challenges in STXBP1 syndrome research, focusing on advanced therapeutic approaches and experimental models. We explore gene therapy strategies, including CRISPR-Cas9, adeno-associated viral (AAV) vectors, and RNA therapies such as antisense oligonucleotides (ASOs), aimed at correcting STXBP1 genetic dysfunctions. This review presents in vivo and in vitro models, highlighting their contributions to understanding disease mechanisms. Additionally, we provide a proposal for a detailed bioinformatic analysis of a Spanish cohort of 41 individuals with STXBP1-related disorders, offering insights into specific mutations and their biological implications. Clinical and translational perspectives are discussed, emphasizing the potential of personalized medicine approaches. Future research directions and key challenges are outlined, including the identification of STXBP1 interactors, unexplored molecular pathways, and the need for clinically useful biomarkers. This comprehensive review underscores the complexity of STXBP1-related infantile epileptic encephalopathy and opens new avenues for advancing the understanding and treatment of this heterogeneous disease.This work was supported by the Asociación Síndrome STXBP1 (España), the Ministerio de Ciencia Innovación y Universidades/Agencia Estatal de Investigación/European Regional Development Fund, UE Grants (RTI2018-099768-B-100; PID2021-127044OB-I00 to A.M. and PID2021-122991NB-C21 to E.F.J.), and Universidad de Jaén (PAIUJA-EI_CTS02_2023)—Junta de Andalucía (BIO-302) to E.F.J.Peer reviewedMultidisciplinary Digital Publishing InstituteAsociación Síndrome STXBP1 (España)Agencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Ministerio de Ciencia e Innovación (España)Junta de AndalucíaUniversidad de JaénÁlvarez-Dolado, Manuel [0000-0002-0655-8289]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/394847https://api.elsevier.com/content/abstract/scopus_id/105001154135reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-099768-B-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127044OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122991NB-C21https://doi.org/10.3390/biotech14010011Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3948472026-05-22T06:33:51Z
dc.title.none.fl_str_mv STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational Research
title STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational Research
spellingShingle STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational Research
Ruano-Rodríguez, Silvestre
STXBP1
Antisense oligonucleotides
Bioinformatics
Epilepsy
Gene and cell therapy
Genomics
Haploinsufficiency
Induced pluripotent stem cells
Infantile epileptic encephalopathy
Murine models
Personalized medicine
title_short STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational Research
title_full STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational Research
title_fullStr STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational Research
title_full_unstemmed STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational Research
title_sort STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational Research
dc.creator.none.fl_str_mv Ruano-Rodríguez, Silvestre
Navarro-Alonso, Mar
Domínguez-Velasco, Benito
Álvarez-Dolado, Manuel
Esteban, Francisco J.
author Ruano-Rodríguez, Silvestre
author_facet Ruano-Rodríguez, Silvestre
Navarro-Alonso, Mar
Domínguez-Velasco, Benito
Álvarez-Dolado, Manuel
Esteban, Francisco J.
author_role author
author2 Navarro-Alonso, Mar
Domínguez-Velasco, Benito
Álvarez-Dolado, Manuel
Esteban, Francisco J.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Asociación Síndrome STXBP1 (España)
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Ministerio de Ciencia e Innovación (España)
Junta de Andalucía
Universidad de Jaén
Álvarez-Dolado, Manuel [0000-0002-0655-8289]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv STXBP1
Antisense oligonucleotides
Bioinformatics
Epilepsy
Gene and cell therapy
Genomics
Haploinsufficiency
Induced pluripotent stem cells
Infantile epileptic encephalopathy
Murine models
Personalized medicine
topic STXBP1
Antisense oligonucleotides
Bioinformatics
Epilepsy
Gene and cell therapy
Genomics
Haploinsufficiency
Induced pluripotent stem cells
Infantile epileptic encephalopathy
Murine models
Personalized medicine
description STXBP1 syndrome is a severe early-onset epileptic encephalopathy characterized by developmental delay and intellectual disability. This review addresses key challenges in STXBP1 syndrome research, focusing on advanced therapeutic approaches and experimental models. We explore gene therapy strategies, including CRISPR-Cas9, adeno-associated viral (AAV) vectors, and RNA therapies such as antisense oligonucleotides (ASOs), aimed at correcting STXBP1 genetic dysfunctions. This review presents in vivo and in vitro models, highlighting their contributions to understanding disease mechanisms. Additionally, we provide a proposal for a detailed bioinformatic analysis of a Spanish cohort of 41 individuals with STXBP1-related disorders, offering insights into specific mutations and their biological implications. Clinical and translational perspectives are discussed, emphasizing the potential of personalized medicine approaches. Future research directions and key challenges are outlined, including the identification of STXBP1 interactors, unexplored molecular pathways, and the need for clinically useful biomarkers. This comprehensive review underscores the complexity of STXBP1-related infantile epileptic encephalopathy and opens new avenues for advancing the understanding and treatment of this heterogeneous disease.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/394847
https://api.elsevier.com/content/abstract/scopus_id/105001154135
url http://hdl.handle.net/10261/394847
https://api.elsevier.com/content/abstract/scopus_id/105001154135
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-099768-B-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127044OB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122991NB-C21
https://doi.org/10.3390/biotech14010011
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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repository.mail.fl_str_mv
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