ArticlePloS one2017
Cas9/gRNA targeted excision of cystic fibrosis-causing deep-intronic splicing mutations restores normal splicing of CFTR mRNA.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline 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
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Genetically engineered approaches to the treatment of cystic fibrosis.Biophysical reviews · 2025Review
- Splicing QTL mapping in stimulated macrophages associates low-usage splice junctions with immune-mediated disease risk.Nature communications · 2025Article
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- The Interface of Gene Editing with Regenerative Medicine.Engineering (Beijing, China) · 2025Article
- Lipopeptide-mediated Cas9 RNP delivery: A promising broad therapeutic strategy for safely removing deep-intronic variants inMolecular therapy. Nucleic acids · 2024Article
- Temporal restriction of Cas9 expression improves CRISPR-mediated deletion efficacy and fidelity.Molecular therapy. Nucleic acids · 2024Article
- Functional Consequences of CFTR Interactions in Cystic Fibrosis.International journal of molecular sciences · 2024Review
- Genetic surgery for a cystic fibrosis-causing splicing mutation.Molecular therapy. Methods & clinical development · 2024Article
- Molecular and functional correction of a deep intronic splicing mutation inMolecular therapy. Methods & clinical development · 2023Article
- Use of adenine base editing and homology-independent targeted integration strategies to correct the cystic fibrosis causing variant, W1282X.Human molecular genetics · 2023Article
- Functional restoration of a CFTR splicing mutation through RNA delivery of CRISPR adenine base editor.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Genome Editing for Cystic Fibrosis.Cells · 2023Review
- SpliceTools, a suite of downstream RNA splicing analysis tools to investigate mechanisms and impact of alternative splicing.Nucleic acids research · 2023Article
- Cystic Fibrosis Screen Positive, Inconclusive Diagnosis Genotypes in People with Cystic Fibrosis from the U.S. Patient Registry.Annals of the American Thoracic Society · 2023Article
- Advances in CRISPR therapeutics.Nature reviews. Nephrology · 2023Review
- Genetic variants in taste genes play a role in oral microbial composition and severe early childhood caries.iScience · 2022Article
- Splicing mutations in the CFTR gene as therapeutic targets.Gene therapy · 2022Review
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic Fibrosis is an autosomal recessive disorder caused by mutations in the CFTR gene. CRISPR mediated, template-dependent homology-directed gene editing has been used to correct the most common mutation, c.1521_1523delCTT / p.Phe508del (F508del) which affects ~70% of individuals, but the efficiency was relatively low. Here, we describe a high efficiency strategy for editing of three different rare CFTR mutations which together account for about 3% of individuals with Cystic Fibrosis. The mutations cause aberrant splicing of CFTR mRNA due to the creation of cryptic splice signals that result in the formation of pseudoexons containing premature stop codons c.1679+1634A>G (1811+1.6kbA>G) and c.3718-2477C>T (3849+10kbC>T), or an out-of-frame 5' extension to an existing exon c.3140-26A>G (3272-26A>G). We designed pairs of Cas9 guide RNAs to create targeted double-stranded breaks in CFTR either side of each mutation which resulted in high efficiency excision of the target genomic regions via non-homologous end-joining repair. When evaluated in a mini-gene splicing assay, we showed that targeted excision restored normal splicing for all three mutations. This approach could be used to correct aberrant splicing signals or remove disruptive transcription regulatory motifs caused by deep-intronic mutations in a range of other genetic disorders.
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