ArticleNucleic acids research2011
Design principles for bifunctional targeted oligonucleotide enhancers of splicing.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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
24 citing papers in PubMed, 42 citations in OpenAlex.
- Strategies for programmable manipulation of alternative splicing.Current opinion in genetics & development · 2024Review
- Unearthing a novel function of SRSF1 in binding and unfolding of RNA G-quadruplexes.Nucleic acids research · 2024Article
- Optimization of Bifunctional Antisense Oligonucleotides for Regulation of Mutually Exclusive Alternative Splicing ofMolecules (Basel, Switzerland) · 2022Article
- Design of Bifunctional Antisense Oligonucleotides for Exon Inclusion.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease.Frontiers in genetics · 2020Review
- The mechanisms of a mammalian splicing enhancer.Nucleic acids research · 2018Article
- Impact, Characterization, and Rescue of Pre-mRNA Splicing Mutations in Lysosomal Storage Disorders.Genes · 2018Review
- Antisense Oligonucleotide-Based Therapy for Neuromuscular Disease.Molecules (Basel, Switzerland) · 2017Review
- Diverse role of survival motor neuron protein.Biochimica et biophysica acta. Gene regulatory mechanisms · 2017Review
- High-Throughput Assays to Assess the Functional Impact of Genetic Variants: A Road Towards Genomic-Driven Medicine.Clinical and translational science · 2017Review
- Review
- ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy.Translational neuroscience · 2017Article
- Article
- Repeated low doses of morpholino antisense oligomer: an intermediate mouse model of spinal muscular atrophy to explore the window of therapeutic response.Human molecular genetics · 2015Article
- RNA-Binding Proteins: Splicing Factors and Disease.Biomolecules · 2015Review
- Splice-correction strategies for treatment of X-linked agammaglobulinemia.Current allergy and asthma reports · 2015Review
- Mechanistic principles of antisense targets for the treatment of spinal muscular atrophy.Future medicinal chemistry · 2015Review
- A targeted oligonucleotide enhancer of SMN2 exon 7 splicing forms competing quadruplex and protein complexes in functional conditions.Cell reports · 2014Article
- Splicing factor TRA2B is required for neural progenitor survival.The Journal of comparative neurology · 2014Article
- Alternative splicing: functional diversity among voltage-gated calcium channels and behavioral consequences.Biochimica et biophysica acta · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 4 countries.
Funding
Abstract
Controlling the patterns of splicing of specific genes is an important goal in the development of new therapies. We have shown that the splicing of a refractory exon, SMN2 exon 7, could be increased in fibroblasts derived from patients with spinal muscular atrophy by using bifunctional targeted oligonucleotide enhancers of splicing (TOES) oligonucleotides that anneal to the exon and contain a 'tail' of enhancer sequences that recruit activating proteins. We show here that there are striking agreements between the effects of oligonucleotides on splicing in vitro and on both splicing and SMN2 protein expression in patient-derived fibroblasts, indicating that the effects on splicing are the major determinant of success. Increased exon inclusion depends on the number, sequence and chemistry of the motifs that bind the activator protein SRSF1, but it is not improved by increasing the strength of annealing to the target site. The optimal oligonucleotide increases protein levels in transfected fibroblasts by a mean value of 2.6-fold (maximum 4.6-fold), and after two rounds of transfection the effect lasted for a month. Oligonucleotides targeted to the upstream exon (exon 6 in SMN) are also effective. We conclude that TOES oligonucleotides are highly effective reagents for restoring the splicing of refractory exons and can act across long introns.
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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.