ArticlePloS one2009
MECP2 isoform-specific vectors with regulated expression for Rett syndrome gene therapy.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays.International journal of molecular sciences · 2020Pooled it
- miRNA modules for precise, tunable control of gene expression.bioRxiv : the preprint server for biology · 2025Article
- Rett syndrome: advances in Understanding MeCP2 function, potential gene therapies, and public health implications.Molecular biology reports · 2025Review
- Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside.Journal of translational medicine · 2024Review
- Epigenetics in rare neurological diseases.Frontiers in cell and developmental biology · 2024Review
- Methyl-CpG-Binding Protein 2 Emerges as a Central Player in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders.Cellular and molecular neurobiology · 2023Review
- Novel MECP2 gene therapy is effective in a multicenter study using two mouse models of Rett syndrome and is safe in non-human primates.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- The Epigenetic Reader Methyl-CpG-Binding Protein 2 (MeCP2) Is an Emerging Oncogene in Cancer Biology.Cancers · 2023Review
- MeCP2 Is an Epigenetic Factor That Links DNA Methylation with Brain Metabolism.International journal of molecular sciences · 2023Review
- State-of-the-art therapies for Rett syndrome.Developmental medicine and child neurology · 2023Review
- Advanced genetic therapies for the treatment of Rett syndrome: state of the art and future perspectives.Frontiers in neuroscience · 2023Review
- Differential Sensitivity of the Protein Translation Initiation Machinery and mTOR Signaling toCells · 2022Article
- Lipid-based nanoparticles and RNA as innovative neuro-therapeutics.Frontiers in pharmacology · 2022Review
- Transcriptional Regulation ofBiomolecules · 2021Article
- Patient-derived iPSC modeling of rare neurodevelopmental disorders: Molecular pathophysiology and prospective therapies.Neuroscience and biobehavioral reviews · 2021Review
- Role of DNA Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome Pathobiology and Mechanism of Disease.Biomolecules · 2021Review
- Cell-Type-Specific Gene Inactivation andThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Chronic Ethanol Exposure Alters DNA Methylation in Neural Stem Cells: Role of Mouse Strain and Sex.Molecular neurobiology · 2020Article
- The MeCP2E1/E2-BDNF-Frontiers in cell and developmental biology · 2020Article
- DNA Methylation Contributes to the Differential Expression Levels ofInternational journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRett Syndrome (RTT) is an Autism Spectrum Disorder and the leading cause of mental retardation in females. RTT is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment. Our objective is to develop viral vectors for MECP2 gene transfer into Neural Stem Cells (NSC) and neurons suitable for gene therapy of Rett Syndrome. METHODOLOGY/PRINCIPAL
findingsWe generated self-inactivating (SIN) retroviral vectors with the ubiquitous EF1alpha promoter avoiding known silencer elements to escape stem-cell-specific viral silencing. High efficiency NSC infection resulted in long-term EGFP expression in transduced NSC and after differentiation into neurons. Infection with Myc-tagged MECP2-isoform-specific (E1 and E2) vectors directed MeCP2 to heterochromatin of transduced NSC and neurons. In contrast, vectors with an internal mouse Mecp2 promoter (MeP) directed restricted expression only in neurons and glia and not NSC, recapitulating the endogenous expression pattern required to avoid detrimental consequences of MECP2 ectopic expression. In differentiated NSC from adult heterozygous Mecp2(tm1.1Bird)+/- female mice, 48% of neurons expressed endogenous MeCP2 due to random inactivation of the X-linked Mecp2 gene. Retroviral MECP2 transduction with EF1alpha and MeP vectors rescued expression in 95-100% of neurons resulting in increased dendrite branching function in vitro. Insulated MECP2 isoform-specific lentiviral vectors show long-term expression in NSC and their differentiated neuronal progeny, and directly infect dissociated murine cortical neurons with high efficiency. CONCLUSIONS/SIGNIFICANCE: MeP vectors recapitulate the endogenous expression pattern of MeCP2 in neurons and glia. They have utility to study MeCP2 isoform-specific functions in vitro, and are effective gene therapy vectors for rescuing dendritic maturation of neurons in an ex vivo model of RTT.
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