ArticleHuman gene therapy2008
A negatively acting bifunctional RNA increases survival motor neuron both in vitro and in vivo.
Article in Human gene therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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.
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.
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Optimizing In Vitro Efficacy Assessment of the Antisense Oligonucleotide Nusinersen in Human Cellular Models.Pharmaceutics · 2026Article
- An engineered U7 small nuclear RNA scaffold greatly increases ADAR-mediated programmable RNA base editing.Nature communications · 2025Article
- Strategies for programmable manipulation of alternative splicing.Current opinion in genetics & development · 2024Review
- Optimization of Bifunctional Antisense Oligonucleotides for Regulation of Mutually Exclusive Alternative Splicing ofMolecules (Basel, Switzerland) · 2022Article
- Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease.Frontiers in genetics · 2020Review
- Blocking p62-dependent SMN degradation ameliorates spinal muscular atrophy disease phenotypes.The Journal of clinical investigation · 2018Article
- Antisense Oligonucleotides: Translation from Mouse Models to Human Neurodegenerative Diseases.Neuron · 2017Review
- Review
- Developing therapies for spinal muscular atrophy.Annals of the New York Academy of Sciences · 2016Review
- Spinal Muscular Atrophy.Neurologic clinics · 2015Review
- Mechanistic principles of antisense targets for the treatment of spinal muscular atrophy.Future medicinal chemistry · 2015Review
- Morpholino antisense oligonucleotides targeting intronic repressor Element1 improve phenotype in SMA mouse models.Human molecular genetics · 2014Article
- Pharmacology of a central nervous system delivered 2'-O-methoxyethyl-modified survival of motor neuron splicing oligonucleotide in mice and nonhuman primates.The Journal of pharmacology and experimental therapeutics · 2014Article
- Dual masking of specific negative splicing regulatory elements resulted in maximal exon 7 inclusion of SMN2 gene.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Redirecting splicing with bifunctional oligonucleotides.Nucleic acids research · 2014Article
- Absence of an intron splicing silencer in porcine Smn1 intron 7 confers immunity to the exon skipping mutation in human SMN2.PloS one · 2014Article
- Applicability of histone deacetylase inhibition for the treatment of spinal muscular atrophy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2013Review
- Recent developments in the treatment of Duchenne muscular dystrophy and spinal muscular atrophy.Therapeutic advances in neurological disorders · 2013Article
- Antisense oligonucleotides for the treatment of spinal muscular atrophy.Human gene therapy · 2013Review
- SMN-inducing compounds for the treatment of spinal muscular atrophy.Future medicinal chemistry · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder and is the leading genetic cause of infant mortality. SMA is caused by the loss of survival motor neuron-1 (SMN1). In humans, a nearly identical copy gene is present called SMN2, but this gene cannot compensate for the loss of SMN1 because of a single silent nucleotide difference in SMN2 exon 7. This single-nucleotide difference attenuates an exonic splice enhancer, resulting in the production of an alternatively spliced isoform lacking exon 7, which is essential for protein function. SMN2, however, is a critical disease modifier and is an outstanding target for therapeutic intervention because all SMA patients retain SMN2 and SMN2 maintains the same coding sequence as SMN1. Therefore, compounds or molecules that increase SMN2 exon 7 inclusion hold great promise for SMA therapeutics. Bifunctional RNAs have been previously used to increase SMN protein levels and derive their name from the presence of two domains: an antisense RNA sequence specific to the target RNA and an untethered RNA segment that serves as a binding platform for splicing factors. This study was designed to develop negatively acting bifunctional RNAs that recruit hnRNPA1 to exon 8 and block the general splicing machinery from the exon 8. By blocking the downstream splice site, this could competitively favor the inclusion of SMN exon 7 and therefore increase full-length SMN production. Here we identify a bifunctional RNA that stimulated full-length SMN expression in a variety of cell-based assays including SMA patient fibroblasts. Importantly, this molecule was also able to induce SMN expression in a previously described mouse model of SMA and demonstrates a novel therapeutic approach for SMA as well as a variety of diseases caused by a defect in splicing.
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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.