ArticleBrain : a journal of neurology2021
Engineered microRNA-based regulatory element permits safe high-dose miniMECP2 gene therapy in Rett mice.
Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- Variable expression ofProceedings of the National Academy of Sciences of the United States of America · 2024Pooled it
- Evidence Synthesis of Gene Therapy and Gene Editing from Different Disorders-Implications for Individuals with Rett Syndrome: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- RNA-Based Therapeutics in Genetic Neurodevelopmental Disorders: Bridging Molecular Genetics and Precision Medicine.International journal of molecular sciences · 2026Review
- MeCP2 Dosage Control in Rett Syndrome: Non-Coding RNA-Based and Epigenetic Strategies for Safer Gene Therapy.Non-coding RNA · 2026Review
- From Gene to Hope: Rett Syndrome and the Rise of Molecular Therapies.Molecular diagnosis & therapy · 2026Review
- Organoids - the future of pre-clinical development of AAV gene therapy for CNS disorders.Gene therapy · 2026Review
- Long-term comparative analysis of AAV9-mediated gene replacement therapies for spinal muscular atrophy in mice.Nature communications · 2026Article
- Modulating alternative splicing ofScience translational medicine · 2026Article
- Lafora disease gene therapy: EPM2A but not EPM2B overexpression results in Lafora body formation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Recent advances in epigenetic therapeutics for Rett syndrome: from mechanisms to clinical trials.Frontiers in behavioral neuroscience · 2026Review
- rAAV9 vector biodistribution in nonhuman primate brain and spinal cord following lumbar intrathecal infusion.Frontiers in medicine · 2026Article
- Genetic and environmental influences in autism: guiding the future of tailored early detection and intervention.The Journal of clinical investigation · 2025Article
- Xist condensates: perspectives for therapeutic intervention.Genome biology · 2025Review
- Neutralizing Antibodies: Role in Immune Response and Viral Vector Based Gene Therapy.International journal of molecular sciences · 2025Review
- Gene regulation technologies for gene and cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Gene therapy then and now: A look back at changes in the field over the past 25 years.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Expression and distribution of rAAV9 intrathecally administered in juvenile to adolescent mice.Gene therapy · 2025Article
- State-of-the-art gene therapy in epilepsy.Current opinion in neurology · 2025Review
- Intravenous esketamine in pediatric Rett syndrome: An open-label, early phase 1 pilot study.Molecular therapy. Methods & clinical development · 2025Article
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
MECP2 gene transfer has been shown to extend the survival of Mecp2-/y knockout mice modelling Rett syndrome, an X-linked neurodevelopmental disorder. However, controlling deleterious overexpression of MECP2 remains the critical unmet obstacle towards a safe and effective gene therapy approach for Rett syndrome. A recently developed truncated miniMECP2 gene has also been shown to be therapeutic after AAV9-mediated gene transfer in knockout neonates. We show that AAV9/miniMECP2 has a similar dose-dependent toxicity profile to that of a published second-generation AAV9/MECP2 vector after treatment in adolescent mice. To overcome that toxicity, we developed a risk-driven viral genome design strategy rooted in high-throughput profiling and genome mining to rationally develop a compact, synthetic microRNA target panel (miR-responsive auto-regulatory element, 'miRARE') to minimize the possibility of miniMECP2 transgene overexpression in the context of Rett syndrome gene therapy. The goal of miRARE is to have a built-in inhibitory element responsive to MECP2 overexpression. The data provided herein show that insertion of miRARE into the miniMECP2 gene expression cassette greatly improved the safety of miniMECP2 gene transfer without compromising efficacy. Importantly, this built-in regulation system does not require any additional exogenous drug application, and no miRNAs are expressed from the transgene cassette. Although broad applications of miRARE have yet to be determined, the design of miRARE suggests a potential use in gene therapy approaches for other dose-sensitive genes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.