ArticleBMC molecular biology2007
Antisense oligonucleotide-induced alternative splicing of the APOB mRNA generates a novel isoform of APOB.
Article in BMC molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Common SNPs in HMGCR in micronesians and whites associated with LDL-cholesterol levels affect alternative splicing of exon13.Arteriosclerosis, thrombosis, and vascular biology · 2008Pooled it
- Impact of mRNA and protein isoforms in lipoprotein metabolism and how to modulate them.Current opinion in lipidology · 2026Review
- Review
- Nuclear and Cytoplasmatic Quantification of Unconjugated, Label-Free Locked Nucleic Acid Oligonucleotides.Nucleic acid therapeutics · 2020Article
- Targeted exon skipping with AAV-mediated split adenine base editors.Cell discovery · 2019Article
- CRISPR-SKIP: programmable gene splicing with single base editors.Genome biology · 2018Article
- Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids.Journal of visualized experiments : JoVE · 2017Article
- Review
- Correlating In Vitro Splice Switching Activity With Systemic In Vivo Delivery Using Novel ZEN-modified Oligonucleotides.Molecular therapy. Nucleic acids · 2014Article
- Development of therapeutic splice-switching oligonucleotides.Human gene therapy · 2014Review
- Splicing modulation therapy in the treatment of genetic diseases.The application of clinical genetics · 2014Review
- Directing HER4 mRNA expression towards the CYT2 isoform by antisense oligonucleotide decreases growth of breast cancer cells in vitro and in vivo.British journal of cancer · 2013Article
- Exon skipping of hepatic APOB pre-mRNA with splice-switching oligonucleotides reduces LDL cholesterol in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Multiple tandem splicing silencer elements suppress aberrant splicing within the long exon 26 of the human Apolipoprotein B gene.BMC molecular biology · 2013Article
- Potential therapeutic applications of antisense morpholino oligonucleotides in modulation of splicing in primary immunodeficiency diseases.Journal of immunological methods · 2011Review
- LDLR-Gene therapy for familial hypercholesterolaemia: problems, progress, and perspectives.International archives of medicine · 2010Article
- Therapeutic RNA manipulation in liver disease.Hepatology (Baltimore, Md.) · 2010Review
- Development of apolipoprotein B antisense molecules as a therapy for hyperlipidemia.Current atherosclerosis reports · 2010 · on this mapReview
- Increasing the relative expression of endogenous non-coding Steroid Receptor RNA Activator (SRA) in human breast cancer cells using modified oligonucleotides.Nucleic acids research · 2009Article
- Progress toward therapy with antisense-mediated splicing modulation.Current opinion in molecular therapeutics · 2009Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundApolipoprotein B (APOB) is an integral part of the LDL, VLDL, IDL, Lp(a) and chylomicron lipoprotein particles. The APOB pre-mRNA consists of 29 constitutively-spliced exons. APOB exists as two natural isoforms: the full-length APOB100 isoform, assembled into LDL, VLDL, IDL and Lp(a) and secreted by the liver in humans; and the C-terminally truncated APOB48, assembled into chylomicrons and secreted by the intestine in humans. Down-regulation of APOB100 is a potential therapy to lower circulating LDL and cholesterol levels.
resultsWe investigated the ability of 2'O-methyl RNA antisense oligonucleotides (ASOs) to induce the skipping of exon 27 in endogenous APOB mRNA in HepG2 cells. These ASOs are directed towards the 5' and 3' splice-sites of exon 27, the branch-point sequence (BPS) of intron 26-27 and several predicted exonic splicing enhancers within exon 27. ASOs targeting either the 5' or 3' splice-site, in combination with the BPS, are the most effective. The splicing of other alternatively spliced genes are not influenced by these ASOs, suggesting that the effects seen are not due to non-specific changes in alternative splicing. The skip 27 mRNA is translated into a truncated isoform, APOB87SKIP27.
conclusionThe induction of APOB87SKIP27 expression in vivo should lead to decreased LDL and cholesterol levels, by analogy to patients with hypobetalipoproteinemia. As intestinal APOB mRNA editing and APOB48 expression rely on sequences within exon 26, exon 27 skipping should not affect APOB48 expression unlike other methods of down-regulating APOB100 expression which also down-regulate APOB48.
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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.