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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Main Authors: Silvestre Ruano-Rodríguez, Mar Navarro-Alonso, Benito Domínguez-Velasco, Manuel Álvarez-Dolado, Francisco J. Esteban
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:BioTech
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Online Access:https://www.mdpi.com/2673-6284/14/1/11
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author Silvestre Ruano-Rodríguez
Mar Navarro-Alonso
Benito Domínguez-Velasco
Manuel Álvarez-Dolado
Francisco J. Esteban
author_facet Silvestre Ruano-Rodríguez
Mar Navarro-Alonso
Benito Domínguez-Velasco
Manuel Álvarez-Dolado
Francisco J. Esteban
author_sort Silvestre Ruano-Rodríguez
collection DOAJ
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.
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institution Kabale University
issn 2673-6284
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series BioTech
spelling doaj-art-17e35c0acddd48b9b2f8216031fb29c72025-08-20T03:43:33ZengMDPI AGBioTech2673-62842025-02-011411110.3390/biotech14010011STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational ResearchSilvestre Ruano-Rodríguez0Mar Navarro-Alonso1Benito Domínguez-Velasco2Manuel Álvarez-Dolado3Francisco J. Esteban4Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), CSIC-US-JA-UPO, Américo Vespuccio Avenue 24, Cartuja Scientific and Technological Park, 41092 Seville, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), CSIC-US-JA-UPO, Américo Vespuccio Avenue 24, Cartuja Scientific and Technological Park, 41092 Seville, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), CSIC-US-JA-UPO, Américo Vespuccio Avenue 24, Cartuja Scientific and Technological Park, 41092 Seville, SpainAndalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), CSIC-US-JA-UPO, Américo Vespuccio Avenue 24, Cartuja Scientific and Technological Park, 41092 Seville, SpainSystems Biology Unit, Department of Experimental Biology, University of Jaén, Campus Las Lagunillas s/n, 23071 Jaén, SpainSTXBP1 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.https://www.mdpi.com/2673-6284/14/1/11antisense oligonucleotidesbioinformaticsepilepsygene and cell therapygenomicshaploinsufficiency
spellingShingle Silvestre Ruano-Rodríguez
Mar Navarro-Alonso
Benito Domínguez-Velasco
Manuel Álvarez-Dolado
Francisco J. Esteban
STXBP1 Syndrome: Biotechnological Advances, Challenges, and Perspectives in Gene Therapy, Experimental Models, and Translational Research
BioTech
antisense oligonucleotides
bioinformatics
epilepsy
gene and cell therapy
genomics
haploinsufficiency
title 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_short 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
topic antisense oligonucleotides
bioinformatics
epilepsy
gene and cell therapy
genomics
haploinsufficiency
url https://www.mdpi.com/2673-6284/14/1/11
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