ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Dual masking of specific negative splicing regulatory elements resulted in maximal exon 7 inclusion of SMN2 gene.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Case Report: Atypical motor development in a patient with the mosaic form of Down syndrome and spinal muscular atrophy type 2- long-term observation.Frontiers in genetics · 2024Article
- Development of 2'-O-Methyl and LNA Antisense Oligonucleotides forBiomedicines · 2023Article
- Splice-switch oligonucleotide-based combinatorial platform prioritizes synthetic lethal targets CHK1 and BRD4 against MYC-driven hepatocellular carcinoma.Bioengineering & translational medicine · 2023Article
- Engineered U1 snRNAs to modulate alternatively spliced exons.Methods (San Diego, Calif.) · 2022Article
- High Concentration or Combined Treatment of Antisense Oligonucleotides for Spinal Muscular Atrophy PerturbedGenes · 2022Article
- Nuclear magnetic resonance reveals a two hairpin equilibrium near the 3'-splice site of influenza A segment 7 mRNA that can be shifted by oligonucleotides.RNA (New York, N.Y.) · 2022Article
- Pluripotent Stem Cell-Based Organoid Technologies for Developing Next-Generation Vision Restoration Therapies of Blindness.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2021Review
- Targeting Alternative Splicing as a Potential Therapy for Episodic Ataxia Type 2.Biomedicines · 2020Review
- Disruption of splicing-regulatory elements using CRISPR/Cas9 to rescue spinal muscular atrophy in human iPSCs and mice.National science review · 2020Article
- Molecular Factors Involved in Spinal Muscular Atrophy Pathways as Possible Disease-modifying Candidates.Current genomics · 2018Review
- Induced-Decay of Glycine Decarboxylase Transcripts as an Anticancer Therapeutic Strategy for Non-Small-Cell Lung Carcinoma.Molecular therapy. Nucleic acids · 2017Article
- Application of urine cells in drug intervention for spinal muscular atrophy.Experimental and therapeutic medicine · 2017Article
- How the discovery of ISS-N1 led to the first medical therapy for spinal muscular atrophy.Gene therapy · 2017Review
- Antisense Oligonucleotides: Translation from Mouse Models to Human Neurodegenerative Diseases.Neuron · 2017Review
- Diverse role of survival motor neuron protein.Biochimica et biophysica acta. Gene regulatory mechanisms · 2017Review
- Motor Neuron Gene Therapy: Lessons from Spinal Muscular Atrophy for Amyotrophic Lateral Sclerosis.Frontiers in molecular neuroscience · 2017Review
- ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy.Translational neuroscience · 2017Article
- MYC regulates the core pre-mRNA splicing machinery as an essential step in lymphomagenesis.Nature · 2015Article
- Peptide nanoparticle delivery of charge-neutral splice-switching morpholino oligonucleotides.Nucleic acid therapeutics · 2015Article
- Improving single injection CSF delivery of AAV9-mediated gene therapy for SMA: a dose-response study in mice and nonhuman primates.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
Corrections and comments
- Erratum issuedDwipramono, Zacharias Aloysius [corrected to Pramono, Zacharias Aloysius Dwi]
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal muscular atrophy (SMA) is a fatal autosomal recessive disease caused by survival motor neuron (SMN) protein insufficiency due to SMN1 mutations. Boosting SMN2 expression is a potential therapy for SMA. SMN2 has identical coding sequence as SMN1 except for a silent C-to-T transition at the 6th nucleotide of exon 7, converting a splicing enhancer to a silencer motif. Consequently, most SMN2 transcripts lack exon 7. More than ten putative splicing regulatory elements (SREs) were reported to regulate exon 7 splicing. To investigate the relative strength of each negative SRE in inhibiting exon 7 inclusion, antisense oligonucleotides (AONs) were used to mask each element, and the fold increase of full-length SMN transcripts containing exon 7 were compared. The most potent negative SREs are at intron 7 (in descending order): ISS-N1, 3' splice site of exon 8 (ex8 3'ss) and ISS+100. Dual-targeting AONs were subsequently used to mask two nonadjacent SREs simultaneously. Notably, masking of both ISS-N1 and ex8 3'ss induced the highest fold increase of full-length SMN transcripts and proteins. Therefore, efforts should be directed towards the two elements simultaneously for the development of optimal AONs for SMA therapy.
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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.