The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Functional Repair of CFTR by CRISPR/Cas9 in Intestinal Stem Cell Organoids of Cystic Fibrosis Patients
Open accessAbstract
Single murine and human intestinal stem cells can be expanded in culture over long time periods as genetically and phenotypically stable epithelial organoids. Increased cAMP levels induce rapid swelling of such organoids by opening the cystic fibrosis transmembrane conductor receptor (CFTR). This response is lost in organoids derived from cystic fibrosis (CF) patients. Here we use the CRISPR/Cas9 genome editing system to correct the CFTR locus by homologous recombination in cultured intestinal stem cells of CF patients. The corrected allele is expressed and fully functional as measured in clonally expanded organoids. This study provides proof of concept for gene correction by homologous recombination in primary adult stem cells derived from patients with a single-gene hereditary defect.
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In the citing paper
“The CRISPR-nuclease SpCas9 was harnessed to correct the ΔF508 mutation by homology-directed repair (HDR)22.”
From Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing (2019) · cites this paper as [22]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“providing the first step to advance gene therapy in cystic fibrosis patients with CRISPR.”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [167]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“They demonstrated that once the mutation had been corrected, the function of the CF transmembrane conductor receptor (CFTR) was restored.4”
From What is CRISPR/Cas9? (2016) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Using adult intestinal stem cells obtained from two patients with CF, they successfully corrected the most common mutation causing CF in intestinal organoids.”
From What is CRISPR/Cas9? (2016) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Using CRISPR, researchers were able to correct mutant intestinal stem cells from cystic fibrosis patients and restore their function in vitro [167]”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [167]
The cited source says what the claim attributes to it.
In the citing paper
“In 2013, researchers culture intestinal stem cells from two cystic fibrosis patients and corrected the mutation at the CFTR locus resulting in the expression of the correct gene and full function of the protein.”
From Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing (2021) · cites this paper as [33]
The cited source says what the claim attributes to it.
In the citing paper
“Since then, the potential utility of the application of CRISPR/Cas-9 for cystic fibrosis was established.33”
From Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing (2021) · cites this paper as [33]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“For instance, organoids derived from intestinal epithelial cells of pediatric IBD patients had IBD-specific DNA methylation signatures despite retaining similar morphologies195.”
From Organoids (2022) · cites this paper as [195]
Experimental — accuracy not yet measuredIn the citing paper
“Several groups have also demonstrated in vitro correction of genetic disease genes including CFTR (cystic fibrosis)9, Crygc (cataracts)10 and DMD (Duchenne muscular dystrophy)11 in organoids or mouse zygotes.”
From Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo (2016) · cites this paper as [9]
In the citing paper
“correct the cystic fibrosis transmembrane conductor receptor locus in cultured intestinal stem cells of cystic fibrosis patients (Schwank et al., 2013)”
From Delivering CRISPR: a review of the challenges and approaches (2018) · cites this paper as Schwank et al., 2013
In the citing paper
“CRISPR-Cas9 genome editing has been applied to correct disease-causing mutations in mouse zygotes and human cell lines for cataract5 and cystic fibrosis6”
From Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype (2014) · cites this paper as [6]
In the citing paper
“In human intestinal stem cells collected from patients with cystic fibrosis, the culprit gene cystic fibrosis transmembrane conductance regulator was rectified by homologous recombination during CRISPR-Cas9 genome editing while the pluripotency was retained as demonstrated by formations of organ-like expansions in cell culture.33”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [33]
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Citations
Cites
A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012) · Science · doi:10.1126/science.1225829 · Cited by 17,116
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNA
Riordan, J. R., Rommens, J. M., Kerem, B.-S., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J.-L., et al. (1989) · Science · doi:10.1126/science.2475911 · Cited by 7,418
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
Self-citationDNA targeting specificity of RNA-guided Cas9 nucleases
Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., Li, Y., Fine, E. J., Wu, X., Shalem, O., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2647 · Cited by 4,741
Webb, A. K. (2006) · Cited by 4,369
Identification of the Cystic Fibrosis Gene: Genetic Analysis
Kerem, B.-S., Rommens, J. M., Buchanan, J. A., Markiewicz, D., Cox, T. K., Chakravarti, A., Buchwald, M., & Tsui, L.-C. (1989) · Science · doi:10.1126/science.2570460 · Cited by 4,142
Sato, T., Stange, D. E., Ferrante, M., Vries, R. G. J., van Es, J. H., van den Brink, S., van Houdt, W. J., Pronk, A., van Gorp, J., Siersema, P. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.050 · Cited by 3,753
Self-citationWang, H., Yang, H., Shivalila, C. S., Dawlaty, M. M., Cheng, A. W., Zhang, F., & Jaenisch, R. (2013) · Cell · doi:10.1016/j.cell.2013.04.025 · Cited by 3,495
Identification of the Cystic Fibrosis Gene: Chromosome Walking and Jumping
Rommens, J. M., Iannuzzi, M. C., Kerem, B.-S., Drumm, M. L., Melmer, G., Dean, M. C., Rozmahel, R. F., Cole, J. L., Kennedy, D., Hidaka, N., et al. (1989) · Science · doi:10.1126/science.2772657 · Cited by 3,301
Cited by
Sorted by citations
The new frontier of genome engineering with CRISPR-Cas9
Doudna, J. A., & Charpentier, E. (2014) · Science · doi:10.1126/science.1258096 · Cited by 7,062
“(organoids) harboring the desired, exact genetic change (104).”
Development and Applications of CRISPR-Cas9 for Genome Engineering
Hsu, P. D., Lander, E. S., & Zhang, F. (2014) · Cell · doi:10.1016/j.cell.2014.05.010 · Cited by 5,762
“, 2014), to engineer isogenic ES and iPS cell disease models with specific mutations introduced or corrected, respectively, or in vivo and ex vivo gene correction (Schwank et al., 2013; Wu et al., 2013).”
Modeling Development and Disease with Organoids
Clevers, H. (2016) · Cell · doi:10.1016/j.cell.2016.05.082 · Cited by 3,196
“The corrected allele was fully functional, as demonstrated in clonally expanded organoids (Schwank et al., 2013).”
BackgroundSelf-citationHuman organoids: model systems for human biology and medicine
Kim, J., Koo, B.-K., & Knoblich, J. A. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0259-3 · Cited by 2,187
Self-citationDrost, J., & Clevers, H. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0007-6 · Cited by 1,790
Self-citation
Metadata
- Authors
- Schwank, G., Koo, B.-K., Sasselli, V., Dekkers, J. F., Heo, I., Demircan, T., Sasaki, N., Boymans, S., Cuppen, E., van der Ent, C. K., Nieuwenhuis, E. E. S., Beekman, J. M., & Clevers, H.
- Affiliations
- University Medical Center Utrecht (NL)
- Wilhelmina Children's Hospital (NL)
- Hubrecht Institute for Developmental Biology and Stem Cell Research (NL)
- Corresponding author
- Clevers, Hans
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 13
- Issue
- 6
- Pages
- 653-658
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W1986316308
- Cited by
- 1,424
- References
- 45
- Citations by year
- 2026: 64 · 2025: 74 · 2024: 92 · 2023: 78 · 2022: 105 · 2021: 152 · 2020: 137 · 2019: 120 · 2018: 118 · 2017: 148 · 2016: 150 · 2015: 110 · 2014: 72 · 2013: 3
- FWCI
- 50.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Wellcome Trust (079249, 097922/C/11/Z)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- cystic fibrosis, CFTR, CRISPR/Cas9 genome editing, homologous recombination, gene correction, cAMP signaling, adult stem cells
- MeSH terms
- Adult, Animals, Base Sequence, Cystic Fibrosis, Humans, Intestines, Molecular Sequence Data, Organoids, Stem Cells, Genetic Therapy, RNA Editing, Cystic Fibrosis Transmembrane Conductance Regulator, Mice, Adult Stem Cells, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Associated Proteins
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