ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Functional restoration of a CFTR splicing mutation through RNA delivery of CRISPR adenine base editor.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Pooled it
- CRISPR-Cas9 genome editing: technological advances, delivery strategies and precision engineering of primary cells for therapeutic application in genetic disorders and diabetes mellitus.Molecular biology reports · 2026Review
- Base editing for precision therapeutics.Cell genomics · 2026Review
- CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.Cells · 2026Review
- Organoids in Genetic Disorders: from Disease Modeling to Translational Applications.Stem cell reviews and reports · 2025Review
- Adenine base editing rescues disrupted BCKDH function and reduces BCAAs toxic accumulation in maple syrup urine disease patient iPSC-hepatic organoids.Stem cell research & therapy · 2025Article
- CRISPR-Cas technologies: Emerging tools from research to clinical application.Journal of microbiology (Seoul, Korea) · 2025Review
- The apical mucus layer alters the pharmacological properties of the airway epithelium.The Journal of physiology · 2025Article
- Functional rescue of F508del-CFTR through revertant mutations introduced by CRISPR base editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Cystic Fibrosis Modulator Therapies: Bridging Insights from CF to other Membrane Protein Misfolding Diseases.Israel journal of chemistry · 2024Article
- Prime editing functionally corrects cystic fibrosis-causing CFTR mutations in human organoids and airway epithelial cells.Cell reports. Medicine · 2024Article
- Use of adenine base editing and homology-independent targeted integration strategies to correct the cystic fibrosis causing variant, W1282X.Human molecular genetics · 2023Article
- Protospacer modification improves base editing of a canonical splice site variant and recovery of CFTR function in human airway epithelial cells.Molecular therapy. Nucleic acids · 2023Article
- Applications and Research Advances in the Delivery of CRISPR/Cas9 Systems for the Treatment of Inherited Diseases.International journal of molecular sciences · 2023Review
- The revolution of personalized pharmacotherapies for cystic fibrosis: what does the future hold?Expert opinion on pharmacotherapyArticle
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The 2789+5G>A CFTR mutation is a quite frequent defect causing an aberrant splicing and a non-functional CFTR protein. Here we used a CRISPR adenine base editing (ABE) approach to correct the mutation in the absence of DNA double-strand breaks (DSB). To select the strategy, we developed a minigene cellular model reproducing the 2789+5G>A splicing defect. We obtained up to 70% editing in the minigene model by adapting the ABE to the PAM sequence optimal for targeting 2789+5G>A with a SpCas9-NG (NG-ABE). Nonetheless, the on-target base correction was accompanied by secondary (bystander) A-to-G conversions in nearby nucleotides, which affected the wild-type CFTR splicing. To decrease the bystander edits, we used a specific ABE (NG-ABEmax), which was delivered as mRNA. The NG-ABEmax RNA approach was validated in patient-derived rectal organoids and bronchial epithelial cells showing sufficient gene correction to recover the CFTR function. Finally, in-depth sequencing revealed high editing precision genome-wide and allele-specific correction. Here we report the development of a base editing strategy to precisely repair the 2789+5G>A mutation resulting in restoration of the CFTR function, while reducing bystander and off-target activities.
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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 Socratic graph.