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Virus-based Gene Therapy Research / CRISPR and Genetic Engineering / Autism Spectrum Disorder Research · Journal article
Neuropsychobiology · August 7, 2026
Early or partial results. Treat as a signal, not a conclusion.
This scoping review identifies 21 preclinical studies demonstrating that gene therapy targeting high-confidence ASD-linked genes (UBE3A, MECP2, FMR1, SHANK3/2, SCN2A, SYNGAP1) achieves molecular correction and behavioral improvements in rodent models across developmental and adult timepoints. No completed human clinical trials exist; significant translational barriers including delivery, safety, and ethical concerns remain unresolved.
Scoping review following PRISMA-ScR framework. Eligible studies: preclinical or translational investigations of gene therapy for ASD-linked genes. Excluded: non-gene-therapy studies, unrelated conditions, reviews, non-English publications.. Intervention: Gene therapy modalities including AAV vectors, antisense oligonucleotides (ASOs), and CRISPR-based editing targeting ASD-linked genes (UBE3A, MECP2, FMR1, SHANK3/2, SCN2A, SYNGAP1). n = 12.
21 preclinical studies identified targeting ASD-linked genes; most demonstrated molecular correction and improvements in synaptic, electrophysiological, and behavioral outcomes 12 translational studies examined delivery innovations (engineered viral capsids, nanoparticles), safety concerns (immune responses, dose-dependent toxicities), and ethical considerations (pediatric consent, neurodiversity perspectives, equity) Therapeutic effects observed from early developmental to adult timepoints in preclinical models
12 translational studies examined delivery innovations (engineered viral capsids, nanoparticles), safety concerns (immune responses, dose-dependent toxicities), and ethical considerations (pediatric consent, neurodiversity perspectives, equity)
Clinicians should recognize gene therapy as a promising preclinical approach for monogenic ASD forms, but must recognize that no human evidence exists yet and substantial translational barriers (delivery, safety, ethical frameworks) remain before clinical application. Current clinical practice should not change based on this evidence.
This scoping review synthesizes preclinical evidence showing molecular and behavioral improvements in rodent models of monogenic ASD, but explicitly notes absence of completed human trials and significant translational barriers, limiting practice applicability.
As stated by the source record.
Quoted from the source exactly as published.
Clinicians should recognize gene therapy as a promising preclinical approach for monogenic ASD forms, but must recognize that no human evidence exists yet and substantial translational barriers (delivery, safety, ethical frameworks) remain before clinical application. Current clinical practice should not change based on this evidence.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
BACKGROUND: Autism spectrum disorder (ASD) lacks disease-modifying therapies. Gene therapy offers a promising avenue to target the underlying molecular causes of ASD, particularly in monogenic or syndromic forms where single-gene mutations play a central role. METHODS: A scoping review was conducted following the PRISMA-ScR framework. We searched PubMed, Scopus, Web of Science, PsycINFO, and the Cochrane Library (2000-July 2025), with the last search completed in July 2025. Eligible studies included preclinical or translational investigations involving gene-therapy modalities (e.g., AAV vectors, ASOs, CRISPR-based editing) targeting high-confidence ASD-linked genes; non-gene-therapy studies, unrelated conditions, reviews, and non-English papers were excluded. Data were charted using a standardized extraction form and synthesized descriptively across two evidence streams. Stream 1 evaluated preclinical studies of gene therapy, while Stream 2 examined translational advances and ethical considerations. RESULTS: Twenty-one preclinical studies were identified in Stream 1, focusing on genes such as UBE3A, MECP2, FMR1, SHANK3/2, SCN2A, and SYNGAP1. Most demonstrated molecular correction and improvements in synaptic, electrophysiological, and behavioral outcomes, with therapeutic effects observed from early developmental to adult timepoints. Stream 2 synthesized 12 studies highlighting translational challenges, including delivery innovations (e.g., engineered viral capsids, nanoparticles), safety concerns (immune responses, dose-dependent toxicities), and ethical considerations (pediatric consent, neurodiversity perspectives, equity in access). Limitations include heterogeneity across models, reliance on rodent studies, and absence of completed human clinical trials. CONCLUSIONS: Gene therapy for ASD shows considerable promise but faces significant translational and ethical hurdles. Standardized study designs, comprehensive safety evaluation, and transparent stakeholder engagement will be critical for developing responsible and effective clinical applications.
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