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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Detalles Bibliográficos
Autores: Ruano-Rodríguez, Silvestre, Navarro-Alonso, Mar, Domínguez-Velasco, Benito, Álvarez-Dolado, Manuel, Esteban, Francisco J.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/394847
Acceso en línea:http://hdl.handle.net/10261/394847
https://api.elsevier.com/content/abstract/scopus_id/105001154135
Access Level:acceso abierto
Palabra clave:STXBP1
Antisense oligonucleotides
Bioinformatics
Epilepsy
Gene and cell therapy
Genomics
Haploinsufficiency
Induced pluripotent stem cells
Infantile epileptic encephalopathy
Murine models
Personalized medicine
Descripción
Sumario: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.