ReviewGene therapy2017
How the discovery of ISS-N1 led to the first medical therapy for spinal muscular atrophy.
Review in Gene therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 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
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 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
- Nusinersen: the antisense oligonucleotide at the forefront of spinal muscular atrophy treatment.RNA biology · 2026Review
- Harnessing CRISPR-dCas13Rx to identify novel antisense targets for therapeutic splicing modulation.Molecular therapy. Nucleic acids · 2026Article
- A historical perspective on the development of antisense oligonucleotide treatments for Duchenne muscular dystrophy and spinal muscular atrophy.Journal of neuromuscular diseases · 2026Review
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- A therapeutic antisense oligonucleotide encompassing 2'-NAR molecular medicine · 2026Article
- Review
- A Chemically Induced CRISPR/dCas13Journal of medicinal chemistry · 2025Article
- Intra-amniotic antisense oligonucleotide treatment improves phenotypes in preclinical models of spinal muscular atrophy.Science translational medicine · 2025Article
- Review
- A Manual for Genome and Transcriptome Engineering.IEEE reviews in biomedical engineering · 2025Review
- Pre-mRNA Splicing Modulation by Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2025Article
- 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
- Patient-specific responses toMolecular therapy. Methods & clinical development · 2024Article
- Quantifying and mitigating motor phenotypes induced by antisense oligonucleotides in the central nervous system.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Nucleic acid drugs: recent progress and future perspectives.Signal transduction and targeted therapy · 2024Review
- Review
- Recent Progress in Gene-Targeting Therapies for Spinal Muscular Atrophy: Promises and Challenges.Genes · 2024Review
- Potential of Cell-Penetrating Peptide-Conjugated Antisense Oligonucleotides for the Treatment of SMA.Molecules (Basel, Switzerland) · 2024Review
- CRISPR-dCas13d-based deep screening of proximal and distal splicing-regulatory elements.Nature communications · 2024Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA), a prominent genetic disease of infant mortality, is caused by low levels of survival motor neuron (SMN) protein owing to deletions or mutations of the SMN1 gene. SMN2, a nearly identical copy of SMN1 present in humans, cannot compensate for the loss of SMN1 because of predominant skipping of exon 7 during pre-mRNA splicing. With the recent US Food and Drug Administration approval of nusinersen (Spinraza), the potential for correction of SMN2 exon 7 splicing as an SMA therapy has been affirmed. Nusinersen is an antisense oligonucleotide that targets intronic splicing silencer N1 (ISS-N1) discovered in 2004 at the University of Massachusetts Medical School. ISS-N1 has emerged as the model target for testing the therapeutic efficacy of antisense oligonucleotides using different chemistries as well as different mouse models of SMA. Here, we provide a historical account of events that led to the discovery of ISS-N1 and describe the impact of independent validations that raised the profile of ISS-N1 as one of the most potent antisense targets for the treatment of a genetic disease. Recent approval of nusinersen provides a much-needed boost for antisense technology that is just beginning to realize its potential. Beyond treating SMA, the ISS-N1 target offers myriad potentials for perfecting various aspects of the nucleic-acid-based technology for the amelioration of the countless number of pathological conditions.
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.