ArticleHuman molecular genetics2013
Trans-splicing correction of tau isoform imbalance in a mouse model of tau mis-splicing.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Review
- RNA exon editing: Splicing the way to treat human diseases.Molecular therapy. Nucleic acids · 2024Review
- The six brain-specific TAU isoforms and their role in Alzheimer's disease and related neurodegenerative dementia syndromes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Tau reduction with artificial microRNAs modulates neuronal physiology and improves tauopathy phenotypes in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy.Frontiers in immunology · 2024Review
- Oligomeric, phosphorylated, and truncated tau and spliceosome pathology within the entorhinal-hippocampal connectome across stages of Alzheimer's disease.The Journal of comparative neurology · 2023Article
- Differential splicing of neuronal genes in a Trem2*R47H mouse model mimics alterations associated with Alzheimer's disease.BMC genomics · 2023Article
- Emerging strategies for the genetic dissection of gene functions, cell types, and neural circuits in the mammalian brain.Molecular psychiatry · 2022Review
- SMaRT modulation of tau isoforms rescues cognitive and motor impairments in a preclinical model of tauopathy.Frontiers in bioengineering and biotechnology · 2022Article
- A new non-aggregative splicing isoform of human Tau is decreased in Alzheimer's disease.Acta neuropathologica · 2021Article
- Alternative splicing in Alzheimer's disease.Aging clinical and experimental research · 2021Review
- Targeting Alternative Splicing as a Potential Therapy for Episodic Ataxia Type 2.Biomedicines · 2020Review
- Astrocyte senescence may drive alterations in GFAPα, CDKN2A p14GeroScience · 2019Article
- RNA Splicing and Disease: Animal Models to Therapies.Trends in genetics : TIG · 2019Review
- RNA Trans-Splicing Modulation via Antisense Molecule Interference.International journal of molecular sciences · 2018Article
- Article
- An RNA-targeted therapy for dystrophic epidermolysis bullosa.Nucleic acids research · 2017Article
- Review
- Tau Isoforms Imbalance Impairs the Axonal Transport of the Amyloid Precursor Protein in Human Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- RNA-based therapies for genodermatoses.Experimental dermatology · 2017Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Abnormal metabolism of the tau protein is central to the pathogenesis of a number of dementias, including Alzheimer's disease. Aberrant alternative splicing of exon 10 in the tau pre-mRNA resulting in an imbalance of tau isoforms is one of the molecular causes of the inherited tauopathy, FTDP-17. We showed previously in heterologous systems that exon 10 inclusion in tau mRNA could be modulated by spliceosome-mediated RNA trans-splicing (SMaRT). Here, we evaluated the potential of trans-splicing RNA reprogramming to correct tau mis-splicing in differentiated neurons in a mouse model of tau mis-splicing, the htau transgenic mouse line, expressing the human MAPT gene in a null mouse Mapt background. Trans-splicing molecules designed to increase exon 10 inclusion were delivered to neurons using lentiviral vectors. We demonstrate reprogramming of tau transcripts at the RNA level after transduction of cultured neurons or after direct delivery and long-term expression of viral vectors into the brain of htau mice in vivo. Tau RNA trans-splicing resulted in an increase in exon 10 inclusion in the mature tau mRNA. Importantly, we also show that the trans-spliced product is translated into a full-length chimeric tau protein. These results validate the potential of SMaRT to correct tau mis-splicing and provide a framework for its therapeutic application to neurodegenerative conditions linked to aberrant RNA processing.
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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.