Genome Editing Strategies for Targeting Synaptic Dysfunction in Neurological Disorders

Genome editing technologies such as CRISPR/Cas9, base editing, and prime editing are rapidly transforming our ability to investigate and treat neurological disorders at the molecular level. Several neuropsychiatric and neurodegenerative conditions such as Alzheimer’s, Parkinson’s, Autism, Schizophrenia, and Epilepsy are now known to involve mutations in genes coding for synaptic proteins. These mutations disrupt synaptic signaling and contribute to disease onset and progression. While traditional drug discovery faces challenges due to the complexity of brain disorders, genome editing offers a precise platform to dissect gene function and restore normal synaptic activity. This research topic aims to explore how genome editing tools can be leveraged to study synaptic dysfunction and enable the development of targeted therapeutics.

Genome editing has revolutionized our capacity to functionally analyze mutations in synaptic genes that contribute to a wide range of neurological conditions such as autism, schizophrenia, and Alzheimer’s disease. Unlike conventional gene knockdown or pharmacological studies, genome editing tools such as CRISPR/Cas9, base editors, and prime editors enable permanent, sequence-specific modifications at the DNA level, offering unprecedented precision to dissect gene function and regulation. This is particularly crucial for synaptic proteins that play context-dependent roles in cognition, emotion, and neuroplasticity, as editing their genes allows researchers to study both cellular mechanisms and behavioral consequences. This Research Topic invites submissions that apply genome editing in diverse systems including animal models, brain organoids, patient-derived induced Pluripotent Stem Cells (iPSCs), and in silico prediction frameworks to interrogate synaptic gene networks. We particularly encourage studies that combine genome editing with single-cell omics, live-cell imaging, and computational modeling to build a more integrative understanding of synaptopathies.

This Research Topic highlights recent advancements in applying genome editing technologies to understand and treat synaptic dysfunction in neurological diseases. We welcome contributions focused on:

• Application of CRISPR, base editors, prime editors, and TALENs to study synaptic genes in vivo and in vitro
• Use of genome-edited human brain organoids to model synaptopathies
• Integration of genome editing with AI/ML-based prediction tools for target identification and validation
• Functional genomics studies targeting synaptic pathways using genome editing platforms
• Therapeutic strategies employing genome editing to correct gene mutations in preclinical disease models

Authors are invited to submit original research articles, reviews, perspectives, and brief communications that address the above themes.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Policy Brief
• Review
• Systematic Review

Keywords: Synaptic Signaling, Neurological Disorders, Gene Mutations, Genome Editing, Biotherapeutics for Neuropathology, CRISPR/Cas9, Base editing

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.