ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
Steric Inhibition of 5' UTR Regulatory Elements Results in Upregulation of Human CFTR.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 43 citations in OpenAlex.
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- PKD1 upstream open reading frames affect Polycystin-1 expression and polycystic kidney disease phenotypes.The Journal of clinical investigation · 2026Article
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- Expanding the toolbox: Emerging antisense oligonucleotide mechanisms for modulating gene expression.Molecular therapy. Nucleic acids · 2026Review
- Targeted BDNF upregulation via upstream open reading frame disruption.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- A rare 5'UTR variant in SEC24D reveals translational dysfunction in osteogenesis imperfecta: a roadmap for RNA therapeutic rescue.Scientific reports · 2026Article
- PKD1 5'UTR variants are a rare cause of disease in ADPKD and suggest a new focus for therapeutic development.European journal of human genetics : EJHG · 2026Article
- RNA diagnostics and therapeutics: a comprehensive review.RNA biology · 2025Review
- Translational regulation of PKD1 by evolutionarily conserved upstream open reading frames.RNA biology · 2025Review
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- Endogenous Ribonucleases: Therapeutic Targeting of the Transcriptome Through Oligonucleotide-Triggered RNA Inactivation.Biomolecules · 2025Review
- uORF-targeting steric block antisense oligonucleotides do not reproducibly increase RNASEH1 expression.Molecular therapy. Nucleic acids · 2025Article
- Exploring precision treatments in immune-mediated inflammatory diseases: Harnessing the infinite potential of nucleic acid delivery.Exploration (Beijing, China) · 2025Review
- Perspectives in MicroRNA Therapeutics for Cystic Fibrosis.Non-coding RNA · 2025Review
- A promoter-dependent upstream activator augments CFTR expression in diverse epithelial cell types.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024Article
- Assembling the RNA therapeutics toolbox.Medical review (2021) · 2024Review
- Possibilities and limitations of antisense oligonucleotide therapies for the treatment of monogenic disorders.Communications medicine · 2024Review
- RNA-Based Vaccines and Therapeutics Against Intracellular Pathogens.Methods in molecular biology (Clifton, N.J.) · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic fibrosis (CF) is an autosomal recessive monogenic disease caused by mutations in the CFTR gene. Therapeutic approaches that are focused on correcting CFTR protein face the challenge of the heterogeneity in CFTR mutations and resulting defects. Thus, while several small molecules directed at CFTR show benefit in the clinic for subsets of CF patients, these drugs cannot treat all CF patients. Additionally, the clinical benefit from treatment with these modulators could be enhanced with novel therapies. To address this unmet need, we utilized an approach to increase CFTR protein levels through antisense oligonucleotide (ASO)-mediated steric inhibition of 5' UTR regulatory elements. We identified ASOs to upregulate CFTR protein expression and confirmed the regulatory role of the sites amenable to ASO-mediated upregulation. Two ASOs were investigated further, and both increased CFTR protein expression and function in cell lines and primary human bronchial epithelial cells with distinct CF genotypes. ASO treatment further increased CFTR function in almost all CF genotypes tested on top of treatment with the FDA approved drug Symdeko (ivacaftor and tezacaftor). Thus, we present a novel approach to CFTR therapeutic intervention, through ASO-mediated modulation of translation.
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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.