ArticleNature medicine2021
Systematic screening identifies therapeutic antisense oligonucleotides for Hutchinson-Gilford progeria syndrome.
Article in Nature medicine, 2021. 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 41 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.
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.
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Who cites it
41 citing papers in PubMed, 73 citations in OpenAlex.
- In Vivo Base Editing Partially Rescues Bone Dysplasia in a Mouse Model of Hutchinson-Gilford Progeria Syndrome.Aging cell · 2026Article
- Mutation-agnostic base editing of the progerin farnesylation site rescues Hutchinson-Gilford progeria syndrome phenotypes in neuromuscular organoids.Nature communications · 2026Article
- First Generation Proteolysis Targeting Chimeras (PROTACs) for the Treatment of Progeria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RNA-coupled CRISPR screens reveal ZNF207 as a regulator of LMNA aberrant splicing in progeria.Molecular cell · 2026Article
- Internal cap-initiated translation for efficient protein production from circular mRNA.Nature biotechnology · 2026Article
- Proliferation and Apoptosis Adaptor Protein 15 (PEA15), a Potential Oncogenic Regulator of VHL and HIF1A Identified through Proteomic Analysis in Hepatocellular Carcinoma.Cancer communications (London, England) · 2026Article
- Selection of specific and efficient siRNAs in new cellular model for Hutchinson-Gilford progeria syndrome therapy.Molecular therapy. Nucleic acids · 2025Article
- Sterile inflammation in laminopathies.European journal of cell biology · 2025Review
- Counteracting lysosome defects alleviates the cellular senescence of Hutchinson-Gilford progeria syndrome.Science China. Life sciences · 2025Article
- 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
- Therapeutic RNA cleavage with RfxCas13d in Hutchinson-Gilford progeria syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Review
- Using RNA therapeutics to promote healthy aging.Nature aging · 2025Review
- Current AAV-mediated gene therapy in sensorineural hearing loss.Fundamental research · 2025Review
- Protein isoform-centric therapeutics: expanding targets and increasing specificity.Nature reviews. Drug discovery · 2024Review
- Genetic and pharmacological modulation of lamin A farnesylation determines its function and turnover.Aging cell · 2024Article
- Long lifetime and tissue-specific accumulation of lamin A/C in Hutchinson-Gilford progeria syndrome.The Journal of cell biology · 2024Article
- The secretome atlas of two mouse models of progeria.Aging cell · 2023Article
- Intermediate, but not average: The unusual lives of the nuclear lamin proteins.Current opinion in cell biology · 2023Review
- Progerin, an Aberrant Spliced Form of Lamin A, Is a Potential Therapeutic Target for HGPS.Cells · 2023Review
Corrections and comments
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- Erratum issued
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Hutchinson-Gilford progeria syndrome (HGPS) is a rare, invariably fatal childhood premature aging disorder caused by a pre-messenger RNA (mRNA) splicing defect in the LMNA gene. We used combined in vitro screening and in vivo validation to systematically explore the effects of target sequence, backbone chemistry and mechanism of action to identify optimized antisense oligonucleotides (ASOs) for therapeutic use in HGPS. In a library of 198 ASOs, the most potent ASOs targeted the LMNA exon 12 junction and acted via non-RNase H-mediated mechanisms. Treatment with an optimized lead candidate resulted in extension of lifespan in a mouse model of HGPS. Progerin mRNA levels were robustly reduced in vivo, but the extent of progerin protein reduction differed between tissues, suggesting a long half-life and tissue-specific turnover of progerin in vivo. These results identify a novel therapeutic agent for HGPS and provide insight into the HGPS disease mechanism.
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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.