{
    "abstract": "Gene therapy development, re-engineering, and application to patients hold promise to revolutionize medicine, including therapies for disorders of the brain. Advances in delivery modalities, expression regulation, and improving safety profiles are of critical importance. Additionally, each inherited disorder has its own unique characteristics as to regions and cell types impacted and the temporal dynamics of that impact that are essential for the design of therapeutic design strategies. Here, we review the current state of the art in gene therapies for inherited brain disorders, summarizing key considerations for vector delivery, gene addition, gene silencing, gene editing, and epigenetic editing. We provide examples from animal models, human cell lines, and, where possible, clinical trials. This review also highlights the various tools available to researchers for basic research questions and discusses our views on the current limitations in the field.",
    "authors": [
        {
            "affiliation": "Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.",
            "firstname": "Zaneta",
            "initials": "Z",
            "lastname": "Matuszek"
        },
        {
            "affiliation": "Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Center for Epilepsy and Neurodevelopmental Disorders (ENDD), Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.",
            "firstname": "Brandon L",
            "initials": "BL",
            "lastname": "Brown"
        },
        {
            "affiliation": "Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.",
            "firstname": "Carolyn M",
            "initials": "CM",
            "lastname": "Yrigollen"
        },
        {
            "affiliation": "Department of Neurological Surgery, The Ohio State Wexner Medical Center, Columbus, OH 43210, USA.",
            "firstname": "Megan S",
            "initials": "MS",
            "lastname": "Keiser"
        },
        {
            "affiliation": "Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Center for Epilepsy and Neurodevelopmental Disorders (ENDD), Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: davidsonbl@chop.edu.",
            "firstname": "Beverly L",
            "initials": "BL",
            "lastname": "Davidson"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025 The Author(s). Published by Elsevier Inc. All rights reserved.",
    "doi": "10.1016/j.ymthe.2025.03.057",
    "journal": "Molecular therapy : the journal of the American Society of Gene Therapy",
    "keywords": [
        "AAV",
        "CRISPR",
        "gene therapy",
        "genome editing",
        "miRNA",
        "neurological treatment",
        "prime editing"
    ],
    "methods": null,
    "publication_date": "2025-04-04",
    "pubmed_id": "40181540",
    "results": null,
    "title": "Current trends in gene therapy to treat inherited disorders of the brain.",
    "xml": "<Element 'PubmedArticle' at 0x788505991f80>"
}