ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Trans-splicing-mediated improvement in a severe mouse model of spinal muscular atrophy.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Systematic review and meta-analysis determining the benefits of in vivo genetic therapy in spinal muscular atrophy rodent models.Gene therapy · 2022Pooled it
- RNAMolecular therapy. Nucleic acids · 2025Article
- Epigenetic Regulation and Therapeutic Targeting of Alternative Splicing Dysregulation in Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Review
- RNA exon editing: Splicing the way to treat human diseases.Molecular therapy. Nucleic acids · 2024Review
- Programmable RNA writing with trans-splicing.bioRxiv : the preprint server for biology · 2024Article
- Article
- Splicing mutations in the CFTR gene as therapeutic targets.Gene therapy · 2022Review
- 5'RNAInternational journal of molecular sciences · 2022Article
- RNA-based therapeutics for neurological diseases.RNA biology · 2022Review
- Therapeutic applications of trans-splicing.British medical bulletin · 2020Article
- Targeting Alternative Splicing as a Potential Therapy for Episodic Ataxia Type 2.Biomedicines · 2020Review
- Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease.Frontiers in genetics · 2020Review
- Intraperitoneal delivery of a novel drug-like compound improves disease severity in severe and intermediate mouse models of Spinal Muscular Atrophy.Scientific reports · 2019Article
- An ex vivo RNA trans-splicing strategy to correct human generalized severe epidermolysis bullosa simplex.The British journal of dermatology · 2019Article
- RNA Trans-Splicing Modulation via Antisense Molecule Interference.International journal of molecular sciences · 2018Article
- Gene Therapy via Trans-Splicing for LMNA-Related Congenital Muscular Dystrophy.Molecular therapy. Nucleic acids · 2018Article
- An RNA-targeted therapy for dystrophic epidermolysis bullosa.Nucleic acids research · 2017Article
- SMN deficiency negatively impacts red pulp macrophages and spleen development in mouse models of spinal muscular atrophy.Human molecular genetics · 2017Article
- Review
- Optimization ofFrontiers in neuroscience · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Spinal muscular atrophy is a leading genetic cause of infantile death and occurs in approximately 1/6000 live births. SMA is caused by the loss of Survival Motor Neuron-1 (SMN1), however, all patients retain at least one copy of a nearly identical gene called SMN2. While SMN2 and SMN1 are comprised of identical coding sequences, the majority of SMN2 transcripts are alternatively spliced, encoding a truncated protein that is unstable and nonfunctional. Considerable effort has focused upon modulating the SMN2 alternative splicing event since this would produce more wild-type protein. Recently we reported the development of an optimized trans-splicing system that involved the coexpression of a SMN2 trans-splicing RNA and an antisense RNA that blocks a downstream splice site in SMN2 pre-mRNA. Here, we demonstrate that in vivo delivery of the optimized trans-splicing vector increases an important SMN-dependent activity, snRNP assembly, in disease-relevant tissue in the SMA mouse model. A single injection of the vector into the intracerebral-ventricular space in SMA neonates also lessens the severity of the SMA phenotype in a severe SMA mouse model, extending survival approximately 70%. Collectively, these results provide the first in vivo demonstration that SMN2 trans-splicing leads to a lessening of the severity of the SMA phenotype and provide evidence for the power of this strategy for reprogramming genetic diseases at the pre-mRNA level.
Indexed as
Identifiers
What OpenQuestion holds
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.