ArticleNature biomedical engineering2025
Systematic optimization of prime editing for the efficient functional correction of CFTR F508del in human airway epithelial cells.
Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
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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
45 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pooled it
- CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Pooled it
- Prime Editing: An Overview.Methods in molecular biology (Clifton, N.J.) · 2027Review
- Review
- Article
- Enhanced γ-globin reactivation and sickle cell correction through a repressor-to-activator motif switch in theMolecular therapy. Nucleic acids · 2026Article
- Advances in prime editing: Molecular innovations, Large-fragment engineering, and AI-driven design.Biodesign research · 2026Review
- Multichannel genomic recording of biological information with ENGRAM.Nature protocols · 2026Review
- Programming biology: next-gen AI firms raise billions to design better medicines.Nature biotechnology · 2026Article
- A primer on prime: A prime editing update from advances to first-in-human trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Considerations for early life genetic therapies in cystic fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Programmable large-cargo integration: Overcoming size constraints for next-generation gene therapy.Synthetic and systems biotechnology · 2026Review
- Directed evolution of small RNA-stabilizing motifs that improve prime-editing efficiency.Nature biotechnology · 2026Article
- Membrane-resolved epithelial electrophysiology revealed using extracellular electrochemical impedance spectroscopy (EEIS).bioRxiv : the preprint server for biology · 2026Article
- RT-qPCR and split-luciferase assays enable batch standardization and analysis of engineered virus-like particle transduction.Molecular therapy. Advances · 2026Article
- Mechanistic machine learning enables interpretable and generalizable prediction of prime editing outcomes.bioRxiv : the preprint server for biology · 2026Article
- Ecological partitioning enables phage-antibiotic cooperation in a human Pseudomonas infection.Nature communications · 2026Article
- Prime Editing Driven Functional Genomics: Bridging Genotype to Phenotype in the Post-Genomic Era.International journal of molecular sciences · 2026Review
- A comprehensive functional atlas of ALK kinase domain variants reveals resistance landscape to ALK inhibitors.Genome biology · 2026Article
- Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Prime editing (PE) enables precise and versatile genome editing without requiring double-stranded DNA breaks. Here we describe the systematic optimization of PE systems to efficiently correct human cystic fibrosis (CF) transmembrane conductance regulator (CFTR) F508del, a three-nucleotide deletion that is the predominant cause of CF. By combining six efficiency optimizations for PE-engineered PE guide RNAs, the PEmax architecture, the transient expression of a dominant-negative mismatch repair protein, strategic silent edits, PE6 variants and proximal 'dead' single-guide RNAs-we increased correction efficiencies for CFTR F508del from less than 0.5% in HEK293T cells to 58% in immortalized bronchial epithelial cells (a 140-fold improvement) and to 25% in patient-derived airway epithelial cells. The optimizations also resulted in minimal off-target editing, in edit-to-indel ratios 3.5-fold greater than those achieved by nuclease-mediated homology-directed repair, and in the functional restoration of CFTR ion channels to over 50% of wild-type levels (similar to those achieved via combination treatment with elexacaftor, tezacaftor and ivacaftor) in primary airway cells. Our findings support the feasibility of a durable one-time treatment for CF.
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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.