ArticleThe Journal of clinical investigation2016
Modulation of LMNA splicing as a strategy to treat prelamin A diseases.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 105 citations in OpenAlex.
- Abnormal nuclear morphology in vivo in mouse hair follicle fibroblasts expressing progerin.Biochemical and biophysical research communications · 2026Article
- Mutation-agnostic base editing of the progerin farnesylation site rescues Hutchinson-Gilford progeria syndrome phenotypes in neuromuscular organoids.Nature communications · 2026Article
- Prelamin A in anArteriosclerosis, thrombosis, and vascular biology · 2026Article
- CRISPR-mediated targeting of theMolecular therapy. Advances · 2026Article
- A case report with the progression from atrial fibrillation to complete AV block, heart failure and electrical storm.Journal of geriatric cardiology : JGC · 2026Article
- Selection of specific and efficient siRNAs in new cellular model for Hutchinson-Gilford progeria syndrome therapy.Molecular therapy. Nucleic acids · 2025Article
- LMNA-related cardiomyopathy: From molecular pathology to cardiac gene therapy.Journal of advanced research · 2025Review
- Precise progerin targeting using RfxCas13d: A therapeutic avenue for Hutchinson-Gilford progeria syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Integrative Approaches to Myopathies and Muscular Dystrophies: Molecular Mechanisms, Diagnostics, and Future Therapies.International journal of molecular sciences · 2025Review
- Impact of miR-181a on SIRT1 Expression and Senescence in Hutchinson-Gilford Progeria Syndrome.Diseases (Basel, Switzerland) · 2025Article
- The accumulation of progerin underlies the loss of aortic smooth muscle cells in Hutchinson-Gilford progeria syndrome.Cell death & disease · 2025Article
- Article
- A deep learning model for characterizing protein-RNA interactions from sequences at single-base resolution.Patterns (New York, N.Y.) · 2025Article
- Review
- Protein isoform-centric therapeutics: expanding targets and increasing specificity.Nature reviews. Drug discovery · 2024Review
- Navigating Lipodystrophy: Insights from Laminopathies and Beyond.International journal of molecular sciences · 2024Review
- Progerin forms an abnormal meshwork and has a dominant-negative effect on the nuclear lamina.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies.Aging and disease · 2024Review
- The nexus of long noncoding RNAs, splicing factors, alternative splicing and their modulations.RNA biology · 2024Review
- mCherry on Top: A Positive Read-Out Cellular Platform for Screening DMD Exon Skipping Xenopeptide-PMO Conjugates.Bioconjugate chemistry · 2023Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The alternatively spliced products of LMNA, lamin C and prelamin A (the precursor to lamin A), are produced in similar amounts in most tissues and have largely redundant functions. This redundancy suggests that diseases, such as Hutchinson-Gilford progeria syndrome (HGPS), that are caused by prelamin A-specific mutations could be treated by shifting the output of LMNA more toward lamin C. Here, we investigated mechanisms that regulate LMNA mRNA alternative splicing and assessed the feasibility of reducing prelamin A expression in vivo. We identified an exon 11 antisense oligonucleotide (ASO) that increased lamin C production at the expense of prelamin A when transfected into mouse and human fibroblasts. The same ASO also reduced the expression of progerin, the mutant prelamin A protein in HGPS, in fibroblasts derived from patients with HGPS. Mechanistic studies revealed that the exon 11 sequences contain binding sites for serine/arginine-rich splicing factor 2 (SRSF2), and SRSF2 knockdown lowered lamin A production in cells and in murine tissues. Moreover, administration of the exon 11 ASO reduced lamin A expression in wild-type mice and progerin expression in an HGPS mouse model. Together, these studies identify ASO-mediated reduction of prelamin A as a potential strategy to treat prelamin A-specific diseases.
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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.