ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Exon skipping of hepatic APOB pre-mRNA with splice-switching oligonucleotides reduces LDL cholesterol in vivo.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
What it found
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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
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Association between apolipoprotein B EcoRI polymorphisms and coronary heart disease : A meta-analysis.Wiener klinische Wochenschrift · 2016Pooled it
- Association Between Apolipoprotein B XbaI Polymorphism and Coronary Heart Disease in Han Chinese Population: A Meta-Analysis.Genetic testing and molecular biomarkers · 2016Pooled it
- Expansion of Splice-Switching Therapy with Antisense Oligonucleotides.International journal of molecular sciences · 2025Review
- Protein isoform-centric therapeutics: expanding targets and increasing specificity.Nature reviews. Drug discovery · 2024Review
- Inhibition of Epidermal Growth Factor Receptor Signaling by Antisense Oligonucleotides as a Novel Approach to Epidermal Growth Factor Receptor Inhibition.Nucleic acid therapeutics · 2022Article
- Targeting KIT by frameshifting mRNA transcripts as a therapeutic strategy for aggressive mast cell neoplasms.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Antisense RNA Therapeutics: A Brief Overview.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Review
- Antisense Oligonucleotide-Mediated Exon-skipping Therapies: Precision Medicine Spreading from Duchenne Muscular Dystrophy.JMA journal · 2021Review
- Delivery of oligonucleotides to bone marrow to modulate ferrochelatase splicing in a mouse model of erythropoietic protoporphyria.Nucleic acids research · 2020Article
- Delivery is key: lessons learnt from developing splice-switching antisense therapies.EMBO molecular medicine · 2017Review
- SNPs, linkage disequilibrium, and chronic mountain sickness in Tibetan Chinese.Hypoxia (Auckland, N.Z.) · 2017Article
- Splice-switching antisense oligonucleotides as therapeutic drugs.Nucleic acids research · 2016Review
- Liver Bid suppression for treatment of fibrosis associated with non-alcoholic steatohepatitis.Journal of hepatology · 2016Article
- Development of therapeutic splice-switching oligonucleotides.Human gene therapy · 2014Review
- A chemical view of oligonucleotides for exon skipping and related drug applications.Nucleic acid therapeutics · 2014Review
- Splicing modulation therapy in the treatment of genetic diseases.The application of clinical genetics · 2014Review
- Alternative Splicing of Nrcam Gene in Dorsal Root Ganglion Contributes to Neuropathic Pain.The journal of painArticle
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 3 institutions in 2 countries.
Funding
Abstract
Familial hypercholesterolemia (FH) is a genetic disorder characterized by extremely high levels of plasma low-density lipoprotein (LDL), due to defective LDL receptor-apolipoprotein B (APOB) binding. Current therapies such as statins or LDL apheresis for homozygous FH are insufficiently efficacious at lowering LDL cholesterol or are expensive. Treatments that target APOB100, the structural protein of LDL particles, are potential therapies for FH. We have developed a series of APOB-directed splice-switching oligonucleotides (SSOs) that cause the expression of APOB87, a truncated isoform of APOB100. APOB87, like similarly truncated isoforms expressed in patients with a different condition, familial hypobetalipoproteinemia, lowers LDL cholesterol by inhibiting very low-density lipoprotein (VLDL) assembly and increasing LDL clearance. We demonstrate that these "APO-skip " SSOs induce high levels of exon skipping and expression of the APOB87 isoform, but do not substantially inhibit APOB48 expression in cell lines. A single injection of an optimized APO-skip SSO into mice transgenic for human APOB resulted in abundant exon skipping that persists for >6 days. Weekly treatments generated a sustained reduction in LDL cholesterol levels of 34-51% in these mice, superior to pravastatin in a head-to-head comparison. These results validate APO-skip SSOs as a candidate therapy for FH.
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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.