ArticleRNA biology
A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy.
Article in RNA biology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 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.
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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
98 citing papers in PubMed, 130 citations in OpenAlex.
- Evaluation of SMN protein, transcript, and copy number in the biomarkers for spinal muscular atrophy (BforSMA) clinical study.PloS one · 2012Trial
- Nusinersen: the antisense oligonucleotide at the forefront of spinal muscular atrophy treatment.RNA biology · 2026Review
- Optimizing In Vitro Efficacy Assessment of the Antisense Oligonucleotide Nusinersen in Human Cellular Models.Pharmaceutics · 2026Article
- Enhanced splicing modulation by NMA-modified antisense oligonucleotides.Nucleic acids research · 2026Article
- A therapeutic antisense oligonucleotide encompassing 2'-NAR molecular medicine · 2026Article
- Bridging science and hope: the evolving story of gene therapy for neuromuscular diseases.Frontiers in cell and developmental biology · 2026Review
- Progress and Future Directions in Exon Skipping and Inclusion Therapies: The Landscape of Oligonucleotide-Based Genetic Medicine.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Pre-mRNA Splicing Modulation by Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Improved gene therapy for spinal muscular atrophy in mice using codon-optimized hSMN1 transgene and hSMN1 gene-derived promotor.EMBO molecular medicine · 2024Article
- Assessment of Nuclear Gem Quantity for Evaluating the Efficacy of Antisense Oligonucleotides in Spinal Muscular Atrophy Cells.Methods and protocols · 2024Article
- Development of 2'-O-Methyl and LNA Antisense Oligonucleotides forBiomedicines · 2023Article
- Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy.Nucleic acids research · 2023Article
- RNA Transcript Diversity in Neuromuscular Research.Journal of neuromuscular diseases · 2023Review
- NADPH oxidase 4 inhibition is a complementary therapeutic strategy for spinal muscular atrophy.Frontiers in cellular neuroscience · 2023Article
- Article
- Targeted-Deletion of a Tiny Sequence via Prime Editing to Restore SMN Expression.International journal of molecular sciences · 2022Article
- Review
- Splice modulating oligomers as cancer therapeutics.Genes & cancer · 2022Article
- Structural Context of a Critical Exon of Spinal Muscular Atrophy Gene.Frontiers in molecular biosciences · 2022Review
- Therapeutic Potential of Nucleic Acids when Combined with Extracellular Vesicles.Aging and disease · 2021Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. Most SMA cases are associated with the low levels of SMN owing to deletion of Survival Motor Neuron 1 (SMN1). SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of SMN1 due to predominant skipping of exon 7. Hence, correction of aberrant splicing of SMN2 exon 7 holds the potential for cure of SMA. Here we report an 8-mer antisense oligonucleotide (ASO) to have a profound stimulatory response on correction of aberrant splicing of SMN2 exon 7 by binding to a unique GC-rich sequence located within intron 7 of SMN2. We confirm that the splicing-switching ability of this short ASO comes with a high degree of specificity and reduced off-target effect compared to larger ASOs targeting the same sequence. We further demonstrate that a single low nanomolar dose of this 8-mer ASO substantially increases the levels of SMN and a host of factors including Gemin 2, Gemin 8, ZPR1, hnRNP Q and Tra2-beta1 known to be down-regulated in SMA. Our findings underscore the advantages and unmatched potential of very short ASOs in splicing modulation in vivo.
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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.