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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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“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]
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“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]
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“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]
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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
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Items 401–500 of 999
Unravelling the complex genetics of common kidney diseases: from variants to mechanisms
Sullivan, K. M., & Suszták, K. (2020) · Nature Reviews Nephrology · doi:10.1038/s41581-020-0298-1 · Cited by 52
Recent Advances in CRISPR/Cas9 Delivery Approaches for Therapeutic Gene Editing of Stem Cells
Lotfi, M., Rad, D. M., Mashhadi, S., Ashouri, A., Mojarrad, M., Mozaffari‐Jovin, S., Farrokhi, S., Hashemi, M., Lotfi, M., Warkiani, M. E., et al. (2023) · Stem Cell Reviews and Reports · doi:10.1007/s12015-023-10585-3 · Cited by 54
“Recent studies have employed CRISPR-Cas9 as the most popular gene editing approach to study cystic fibrosis [6, 7], sickle cell disease (SCD) [8, 9], Huntington’s chorea disorder [10, 11], Duchenne muscular dystrophy [12–14], chronic granulomatous disease [15, 16] retinitis pigmentosa [17]…”
Colorectal cancer models for novel drug discovery
Golovko, D. M., Kedrin, D., Yilmaz, Ö. H., & Roper, J. (2015) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2015.1079618 · Cited by 52
Modeling human disease using organotypic cultures
Schweiger, P. J., & Jensen, K. B. (2016) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2016.07.003 · Cited by 53
A Review of CRISPR-Based Genome Editing: Survival, Evolution and Challenges
Ahmad, H. I., Ahmad, M. J., Asif, A. R., Adnan, M., Iqbal, M. K., Mehmood, K., Muhammad, S. A., Bhuiyan, A. A., Elokil, A., Du, X., et al. (2018) · Current Issues in Molecular Biology · doi:10.21775/cimb.028.047 · Cited by 52
The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology
Yu, H. M., Hasan, N. M., In, J., Estes, M. K., Kovbasnjuk, O. N., Zachos, N. C., & Donowitz, M. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105211 · Cited by 51
Harnessing single-cell genomics to improve the physiological fidelity of organoid-derived cell types
Mead, B. E., Ordovás-Montañés, J., Braun, A. P., Levy, L. E., Bhargava, P., Szucs, M. J., Ammendolia, D. A., MacMullan, M. A., Yin, X., Hughes, T. K., et al. (2018) · BMC Biology · doi:10.1186/s12915-018-0527-2 · Cited by 50
“Recent work has demonstrated the utility of organoids in assessing bulk phenotypes that are readily observed and easily selected for, such as phenotypes of cystic fibrosis and the study of cancer-associated mutational signatures [9, 10].”
BackgroundNguyen, R., Bae, S. D. W., Qiao, L., & George, J. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.03.017 · Cited by 53
Animal Models in Biomedical Research
Maurer, K. J., & Quimby, F. W. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-409527-4.00034-1 · Cited by 51
A bioengineering perspective on modelling the intestinal epithelial physiology in vitro
Antfolk, M., & Jensen, K. B. (2020) · Nature Communications · doi:10.1038/s41467-020-20052-z · Cited by 57
Martiniano, S. L., Sagel, S. D., & Zemanick, E. T. (2016) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000000351 · Cited by 50
Han, X., Liu, Z., Ma, Y., Zhang, K., & Qin, L. (2017) · Advanced Biosystems · doi:10.1002/adbi.201600007 · Cited by 50
Science and Bioethics of CRISPR-Cas9 Gene Editing: An Analysis Towards Separating Facts and Fiction.
Cribbs, A. P., & Perera, S. (2017) · PubMed · Cited by 49
Genetic engineering in primary human B cells with CRISPR-Cas9 ribonucleoproteins
Wu, C.-A. M., Roth, T. L., Baglaenko, Y., Ferri, D., Brauer, P. M., Zúñiga‐Pflücker, J. C., Rosbe, K. W., Wither, J., Marson, A., & Allen, C. D. C. (2018) · Journal of Immunological Methods · doi:10.1016/j.jim.2018.03.009 · Cited by 48
CRISPR therapeutic tools for complex genetic disorders and cancer (Review)
Baliou, S., Adamaki, M., Kyriakopoulos, A. M., Spandidos, D. A., Panayiotidis, M. I., Christodoulou, I., & Zoumpourlis, V. C. (2018) · International Journal of Oncology · doi:10.3892/ijo.2018.4434 · Cited by 55
“Cysticfibrosis CFTR HDR-mediated cDNA knock-in Intestinal organoid Schwank et al (82), 2013”
InfluentialMini-gut: a promising model for drug development
Yin, Y., de Jonge, H. R., Wu, X., & Yin, Y. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.06.006 · Cited by 49
Translating Embryogenesis to Generate Organoids: Novel Approaches to Personalized Medicine
Sahu, S., & Sharan, S. K. (2020) · iScience · doi:10.1016/j.isci.2020.101485 · Cited by 52
Ugonotti, J., Chatterjee, S., & Thaysen‐Andersen, M. (2020) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2020.100882 · Cited by 47
Fleischer, A., Vallejo‐Díez, S., Martín‐Fernández, J. M., Sánchez‐Gilabert, A., Castresana, M., del Pozo, Á., Esquisabel, A., Ávila, S., Castrillo, J. L., Gaínza, E., et al. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.04.005 · Cited by 52
Gene therapy for cystic fibrosis: Challenges and prospects
Sui, H., Xu, X., Su, Y., Gong, Z., Yao, M., Liu, X., Zhang, T., Jiang, Z., Bai, T., Wang, J., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1015926 · Cited by 56
“HDR-based CFTR corrections have demonstrated the capacities to correct missense or nonsense mutations in exons, to ablate splice mutations, and to insert “super exons” from the DNA donor template provided along with the CRISPR components (Schwank et al., 2013; Firth et al., 2015).”
BackgroundProgress and Perspective of CRISPR‐Cas9 Technology in Translational Medicine
Zheng, R., Zhang, L., Parvin, R., Su, L., Chi, J., Shi, K., Ye, F., & Huang, X. (2023) · Advanced Science · doi:10.1002/advs.202300195 · Cited by 56
Nabar, N., Dacoba, T. G., Covarrubias, G., Romero-Cruz, D., & Hammond, P. T. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2307809121 · Cited by 54
Morphological profiling for drug discovery in the era of deep learning
Tang, Q., Ratnayake, R., Seabra, G. D. M., Jiang, Z., Fang, R., Cui, L., Ding, Y., Kahveci, T., Bian, J., Li, C., et al. (2024) · Briefings in Bioinformatics · doi:10.1093/bib/bbae284 · Cited by 58
“Defined mutations are introduced to transform normal organoids to tumorigenic growth upon xenotransplantation, combining the exploratory power of CRISPR-Cas9 screening with 3D organoids [133, 136, 141].”
BackgroundFrom Gene Targeting to Genome Editing: Transgenic animals applications and beyond
Rocha-Martins, M., Cavalheiro, G. R., Matos-Rodrigues, G. E., & Martins, R. A. P. (2015) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765201520140710 · Cited by 52
Potential Use of Human Stem Cell-Derived Intestinal Organoids to Study Inflammatory Bowel Diseases.
Dotti, I., & Salas, A. (2018) · Europe PMC (PubMed Central) · doi:10.1093/ibd/izy275 · Cited by 49
Commercialization of Organoids
Choudhury, D., Ashok, A., & Naing, M. W. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.12.002 · Cited by 50
Hu, S., Du, J., Chen, N., Jia, R., Zhang, J., Liu, X., & Yang, L. (2020) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.61.4.31 · Cited by 48
Biobanking of human gut organoids for translational research
Perrone, F. M., & Zilbauer, M. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00606-x · Cited by 54
Establishment of Human Epithelial Enteroids and Colonoids from Whole Tissue and Biopsy
Mahé, M. M., Sundaram, N., Watson, C. L., Shroyer, N. F., & Helmrath, M. A. (2015) · Journal of Visualized Experiments · doi:10.3791/52483-v · Cited by 48
Prime Editing for Human Gene Therapy: Where Are We Now?
Godbout, K., & Tremblay, J. P. (2023) · Cells · doi:10.3390/cells12040536 · Cited by 56
“Still, the efficiency was very low [57].”
Stem cell therapy: a revolutionary cure or a pandora's box
Marei, H. E. S. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04334-1 · Cited by 56
“Similarly, intestinal organoids have been used to investigate the effectiveness of CFTR modulators on patient-specific mutations to explore cystic fibrosis [14].”
Cystic Fibrosis and Its Management Through Established and Emerging Therapies
Spielberg, D. R., & Clancy, J. P. (2016) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090314-050024 · Cited by 48
Potentiator synergy in rectal organoids carrying S1251N, G551D, or F508del CFTR mutations
Dekkers, J. F., van Mourik, P., Vonk, A. M., Kruisselbrink, E., Berkers, G., Groot, K. M. D. W., Janssens, H. M., Bronsveld, I., van der Ent, C. K., de Jonge, H. R., et al. (2016) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2016.04.007 · Cited by 45
Self-citationGene correction in patient-specific iPSCs for therapy development and disease modeling
Jang, Y.-Y., & Ye, Z. (2016) · Human Genetics · doi:10.1007/s00439-016-1691-5 · Cited by 48
“In an earlier and related study, Schwank and colleagues have used the CRISPR system to repair CFTR in intestinal stem cell organoids of cystic fibrosis patients and have demonstrated high specificity of CRISPR/Cas9 in the study (Schwank et al. 2013).”
BackgroundHighly efficient gene inactivation by adenoviral CRISPR/Cas9 in human primary cells
Voets, O., Tielen, F., Elstak, E., Benschop, J., Grimbergen, M., Stallen, J., Janssen, R., van Marle, A., & Essrich, C. (2017) · PLOS ONE · doi:10.1371/journal.pone.0182974 · Cited by 48
Use of CRISPR/Cas9 gene-editing tools for developing models in drug discovery
Ahmad, G., & Amiji, M. M. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.01.014 · Cited by 48
Optimized delivery of siRNA into 3D tumor spheroid cultures in situ
Morgan, R. G., Chambers, A. C., Legge, D. N., Coles, S. J., Greenhough, A., & Williams, A. C. (2018) · Scientific Reports · doi:10.1038/s41598-018-26253-3 · Cited by 47
CRISPR/Cas9 System: A Bacterial Tailor for Genomic Engineering
Lone, B. A., Karna, S. K. L., Ahmad, F., Shahi, N., & Pokharel, Y. R. (2018) · Genetics Research International · doi:10.1155/2018/3797214 · Cited by 48
“This system has successfully corrected genetic diseasecausing mutations in human cell lines for cystic fibrosis [121, 122] and β-thalassemia [123].”
BackgroundCurrent trends in gene recovery mediated by the CRISPR-Cas system
Jang, H., Song, B., Hwang, G., & Bae, S. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0466-1 · Cited by 49
Reconstructing the tumor architecture into organoids
Luo, Z., Zhou, X., Mandal, K., He, N., Wennerberg, W., Qu, M., Jiang, X., Sun, W., & Khademhosseini, A. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113839 · Cited by 49
Bellec, J., Bacchetta, M., Losa, D., Anegón, I., Chanson, M., & Nguyen, T. M. (2015) · Current Gene Therapy · doi:10.2174/1566523215666150812115939 · Cited by 45
“RNAi and genome editing strategies have been successfully used to generate cell and transgenic animal models and for therapeutics purposes [10,11] in various pathologies including cystic fibrosis (CF) [12].”
BackgroundDefining hierarchies of stemness in the intestine: evidence from biomarkers and regulatory pathways
Gracz, A. D., & Magness, S. T. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00066.2014 · Cited by 48
Gene Editing and Genetic Lung Disease. Basic Research Meets Therapeutic Application
Alapati, D., & Morrisey, E. E. (2016) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2016-0301ps · Cited by 47
“CF The Clevers group has shown that intestinal organoids from pediatric patients that are homozygous for CFTR ΔF508 lack the ability to respond to forskolin stimulation by swelling, mimicking important aspects of CF disease in vitro (15).”
BackgroundNoben, M., Vanhove, W., Arnauts, K., Ramalho, A. S., Assche, G. V., Vermeire, S., Verfaillie, C. M., & Ferrante, M. (2017) · United European Gastroenterology Journal · doi:10.1177/2050640617722903 · Cited by 51
“In the cystic fibrosis (CF) field, patient-derived organoids are being used to screen therapeutic compounds using the forskolin swelling assay to determine their potential to rescue cystic fibrosis transmembrane conductance regulator (CFTR) function in a personalised manner.27 Moreover, using CRISPR/Cas9 gene editing,…”
BackgroundCRISPR/Cas9: the Jedi against the dark empire of diseases
Khan, S., Mahmood, M. S., Rahman, S. U., Zafar, H., Khan, S. H., khan, Z., & Ahmad, A. (2018) · Journal of Biomedical Science · doi:10.1186/s12929-018-0425-5 · Cited by 49
“Cystic fibrosis Transfection into intestinal stem cells from patients Correction of CFTR gene mutation (3 substitution) [50] Khan et al.”
Garcia, A. L. C., Arlt, V. M., & Phillips, D. H. (2021) · Mutagenesis · doi:10.1093/mutage/geab023 · Cited by 47
“This has been replicated a number of times from murine and human tissues and adapted for the establishment of intestinal organoids from cystic fibrosis patients (34,52,53).”
Backgroundvan Hees, M., Slott, S., Hansen, A. H., Kim, H. S., Ji, H. P., & Astakhova, K. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.06.003 · Cited by 47
CRISPR Cas system: A strategic approach in detection of nucleic acids
Fapohunda, F. O., Huang, D., Qiu, S., Qiao, S., Pan, Y., Shi, S., Wang, H., & Lü, P. (2022) · Microbiological Research · doi:10.1016/j.micres.2022.127000 · Cited by 46
Toward inclusive therapy with CFTR modulators: Progress and challenges
Guimbellot, J. S., Sharma, J., & Rowe, S. M. (2017) · Pediatric Pulmonology · doi:10.1002/ppul.23773 · Cited by 47
Nasospheroids permit measurements of CFTR-dependent fluid transport
Guimbellot, J. S., Leach, J. M., Chaudhry, I. G., Quinney, N. L., Boyles, S. E., Chua, M., Aban, I., Jaspers, I., & Gentzsch, M. (2017) · JCI Insight · doi:10.1172/jci.insight.95734 · Cited by 44
The ethics of clinical applications of germline genome modification: a systematic review of reasons
van Dijke, I., Bosch, L., Bredenoord, A. L., Cornel, M. C., Repping, S., & Hendriks, S. (2018) · Human Reproduction · doi:10.1093/humrep/dey257 · Cited by 46
“First, GGM could correct disease-causing gene(s), to prevent diseases such as cystic fibrosis (Schwank et al., 2013).”
BackgroundProgrammable Molecular Scissors: Applications of a New Tool for Genome Editing in Biotech
Saha, S. K., Saikot, F. K., Rahman, M. S., Jamal, M. A. H. M., Rahman, S. M. K., Islam, S. M. R., & Kim, K. (2018) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2018.11.016 · Cited by 48
“Fibrosis Reproduced from Schwank et al.(262) Copyright 2013.”
BackgroundMethodInfluentialYadak, R., Breur, M., & Bugiani, M. (2019) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-019-1016-6 · Cited by 46
“Intestinal organoids could be expanded for tissue regeneration or genetically modified by CRISPR/ Cas9 [107] or vector [103] based gene therapy to restore TP, and perhaps supported by tissue engineering would generate viable tissue engineered autologous small intestines and transplanted back into the patient.”
BackgroundPhysiology of Electrolyte Transport in the Gut: Implications for Disease
Rao, M. C. (2019) · Comprehensive physiology · doi:10.1002/cphy.c180011 · Cited by 54
CRISPR/Cas9 and Nanotechnology Pertinence in Agricultural Crop Refinement
Naik, B. J., Shimoga, G. D., Kim, S.-C., Manjulatha, M., Palem, R. R., Palem, R. R., Kumar, M., Kim, S., & Lee, S. (2022) · Frontiers in Plant Science · doi:10.3389/fpls.2022.843575 · Cited by 46
Recent advances in organoid engineering: A comprehensive review
Unagolla, J. M., & Jayasuriya, A. C. (2022) · Applied Materials Today · doi:10.1016/j.apmt.2022.101582 · Cited by 44
McCaughey, T., Budden, D., Sanfilippo, P. G., Gooden, G. E. C., Li, F., Fenwick, E., Rees, G., MacGregor, C., Si, L., Chen, C., et al. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.033 · Cited by 45
Generation of 3D human gastrointestinal organoids: principle and applications
Zhang, M., Liu, Y., & Chen, Y. (2020) · Cell Regeneration · doi:10.1186/s13619-020-00040-w · Cited by 47
Wang, J., Chen, C., Wang, L., Xie, M., Ge, X., Wu, S., He, Y., Mou, X., Ye, C., & Sun, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.872531 · Cited by 46
“In 2013, Hans Clevers’s group was the first to implement CRISPR–Cas9 technology in an organoid model (91).”
BackgroundSuzuki, S., Sargent, R. G., Illek, B., Fischer, H., Esmaeili-Shandiz, A., Yezzi, M. J., Lee, A., Yang, Y., Kim, S., Renz, P., et al. (2016) · Molecular Therapy: Nucleic Acids · doi:10.1038/mtna.2015.43 · Cited by 43
Genome Editing of Monogenic Neuromuscular Diseases
Long, C., Amoasii, L., Bassel‐Duby, R., & Olson, E. N. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.3388 · Cited by 46
From organoids to organs: Bioengineering liver grafts from hepatic stem cells and matrix
Willemse, J., Lieshout, R., van der Laan, L. J. W., & Verstegen, M. M. A. (2017) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2017.03.003 · Cited by 44
Song, M. (2017) · Biotechnology Progress · doi:10.1002/btpr.2484 · Cited by 46
“In 2013, CRISPR/Cas9-mediated genome editing of the cystic fibrosis transmembrane conductor receptor gene (CFTR) was tried.(84) Specifically, intestinal stem cell organoids from CF patients were cultured, and CFTR gene correction occurred via homologous recombination.”
BackgroundKang, X., Caparas, C. I. N., Soh, B.-S., & Fan, Y. (2017) · Protein & Cell · doi:10.1007/s13238-017-0477-4 · Cited by 49
Cosenza, L. C., Gasparello, J., Romanini, N., Zurlo, M., Zuccato, C., Gambari, R., & Finotti, A. (2021) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2021.03.025 · Cited by 43
Induced Pluripotent Stem Cells: Challenges and Opportunities for Cancer Immunotherapy
Sachamitr, P., Hackett, S., & Fairchild, P. J. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00176 · Cited by 41
“Furthermore, their potential for the efficient scale-up of cell production and tractability for new generation genome engineering tools, such as the CRISPR/Cas-9 system and transcription activator-like effector nucleases (TALENs) (48, 49) may herald a new era in cancer immunotherapy, in which treatments are exquisitel…”
BackgroundCystic Fibrosis – a Multiorgan Protein Misfolding Disease
Fraser-Pitt, D. J., & O′Neil, D. A. (2015) · Future Science OA · doi:10.4155/fso.15.57 · Cited by 42
Egan, M. E. (2015) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2015.11.002 · Cited by 49
Using CRISPR/Cas to study gene function and model disease in vivo
Tschaharganeh, D. F., Lowe, S. W., Garippa, R. J., & Livshits, G. (2016) · FEBS Journal · doi:10.1111/febs.13750 · Cited by 47
CRISPR-Mediated Epigenome Editing.
Enríquez, P. (2016) · Europe PMC (PubMed Central) · Cited by 41
PGE2 is a direct and robust mediator of anion/fluid secretion by human intestinal epithelial cells
Fujii, S., Suzuki, K., Kawamoto, A., Ishibashi, F., Nakata, T., Murano, T., Ito, G., Shimizu, H., Mizutani, T., Oshima, S., et al. (2016) · Scientific Reports · doi:10.1038/srep36795 · Cited by 42
García‐Tuñón, I., Hernández‐Sánchez, M., Ordóñez, J. L., Alonso-Pérez, V., Quijada‐Álamo, M., Benito, R., Guerrero, C., Hernández‐Rivas, J. M., & Sánchez‐Martín, M. (2017) · Oncotarget · doi:10.18632/oncotarget.15215 · Cited by 41
CRISPR/Cas9-mediated correction of human genetic disease
Men, K., Duan, X., He, Z., Yang, Y., Yao, S., & Wei, Y. (2017) · Science China Life Sciences · doi:10.1007/s11427-017-9032-4 · Cited by 44
New tools for old drugs: Functional genetic screens to optimize current chemotherapy
Gerhards, N. M., & Rottenberg, S. (2018) · Drug Resistance Updates · doi:10.1016/j.drup.2018.01.001 · Cited by 43
“Organoids can usually be expanded easily, cryopreserved and biobanked and efficiently genetically manipulated (van de Wetering et al., 2015, Schwank et al., 2013, Drost et al., 2017).”
BackgroundExtracellular vesicles transmit epithelial growth factor activity in the intestinal stem cell niche
Oszvald, Á., Szvicsek, Z., Sándor, G. O., Kelemen, A., Soós, A. Á., Pálóczi, K., Bursics, A., Dede, K., Tölgyes, T., Buzás, E. I., et al. (2019) · Stem Cells · doi:10.1002/stem.3113 · Cited by 42
Minimizing off-Target Mutagenesis Risks Caused by Programmable Nucleases
Ishida, K., Gee, P., & Hotta, A. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161024751 · Cited by 41
“The CRISPR Cas9 system also has tremendous therapeutic potential [17] and has been shown to correct genetic mutations [18] such as β-thalassemia [19], cystic fibrosis [20], hemophilia A [21], cataracts [22], hereditary tyrosinemia type I [23], and Duchenne muscular dystrophy [24].”
BackgroundTidball, A. M., & Parent, J. M. (2015) · Stem Cells · doi:10.1002/stem.2203 · Cited by 43
A Notch positive feedback in the intestinal stem cell niche is essential for stem cell self‐renewal
Chen, K., Srinivasan, T., Tung, K., Belmonte, J. M., Wang, L., Murthy, P. K. L., Choi, J., Rakhilin, N., King, S., Varanko, A. K., et al. (2017) · Molecular Systems Biology · doi:10.15252/msb.20167324 · Cited by 43
“CRISPR/Cas9 genomic editing The procedure for CRISPR/Cas9-mediated transfection in mouse ISC organoids has been previously described (Schwank et al, 2013).”
MethodCFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease
Fernández, E. F., Santi, C. D., Rose, V. D., & Greene, C. M. (2018) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2018.1475235 · Cited by 41
In Vitro Models of the Liver: Disease Modeling, Drug Discovery and Clinical Applications
Collins, S. D., Yuen, G., Tu, T., Budzinska, M. A., Spring, K. J., Bryant, K., & Shackel, N. A. (2019) · Codon Publications eBooks · doi:10.15586/hepatocellularcarcinoma.2019.ch3 · Cited by 42
“Another exciting avenue to explore is CRISPR gene editing, with success already achieved using intestinal organoids of cystic fibrosis patients, where the cystic fibrosis transmembrane conductance regulator (CFTR) locus was corrected in vitro by homologous recombination (93).”
BackgroundExploiting CRISPR Cas9 in Three-Dimensional Stem Cell Cultures to Model Disease
Gopal, S., Rodrigues, A. L., & Dordick, J. S. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00692 · Cited by 46
“One of the earliest examples of using CRISPR Cas9 to repair a mutant gene was done using cystic fibrosis transmembrane conductor receptor (CFTR) (Schwank et al., 2013).”
MethodInfluentialRecent Advances in Genome-Engineering Strategies
Boti, M. A., Athanasopoulou, K., Adamopoulos, P. G., Sideris, D. C., & Scorilas, A. (2023) · Genes · doi:10.3390/genes14010129 · Cited by 44
Novel Genome-Editing Tools to Model and Correct Primary Immunodeficiencies
de Bruin, L. M. O., Volpi, S., & Musunuru, K. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00250 · Cited by 44
“The corrected organoids showed swelling in response to forskolin treatment, as expected in the presence of a functional CFTR protein, whereas the mutant organoids failed to swell (85).”
Applications of TALENs and CRISPR/Cas9 in Human Cells and Their Potentials for Gene Therapy
Niu, J., Zhang, B., & Chen, H. (2014) · Molecular Biotechnology · doi:10.1007/s12033-014-9771-z · Cited by 41
“correct the CFTR loci by HDR-repair in cultured intestinal stem cells of cystic fibrosis (CF) patients [56].”
BackgroundCardiac Organoids: A 3D Technology for Modeling Heart Development and Disease
Zhu, L., Liu, K. Y., Feng, Q., & Liao, Y. (2022) · Stem Cell Reviews and Reports · doi:10.1007/s12015-022-10385-1 · Cited by 43
Parihar, A., Pandita, V., & Khan, R. (2022) · Biotechnology and Bioengineering · doi:10.1002/bit.28166 · Cited by 41
CRISPR‐Cas: From the Bacterial Adaptive Immune System to a Versatile Tool for Genome Engineering
Kirchner, M., & Schneider, S. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201504741 · Cited by 39
Emerging gene therapies for cystic fibrosis
Miah, K. M., Hyde, S. C., & Gill, D. R. (2019) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2019.1634547 · Cited by 39
Marotta, N., Kim, S., & Krainc, D. (2020) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2020.1703671 · Cited by 40
“In addition, the use of CRISPR technology in organoids [188] is highly relevant for studying the role of PD”
BackgroundHuman iPSCs and Genome Editing Technologies for Precision Cardiovascular Tissue Engineering
Gähwiler, E. K. N., Motta, S. E., Martin, M., Nugraha, B., Hoerstrup, S. P., & Emmert, M. Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.639699 · Cited by 42
“…and the improvement of hiPSC differentiation protocols with CRISPR-Cas9 gene editing tools have established powerful approaches for SC-related research, human disease modeling, and drug development/screening (Schwank et al., 2013; Johnson and Hockemeyer, 2015; Matano et al., 2015; Musunuru, 2017a).”
MethodCorrection of Airway Stem Cells: Genome Editing Approaches for the Treatment of Cystic Fibrosis
King, N. E., Suzuki, S., Barillà, C., Hawkins, F. J., Randell, S. H., Reynolds, S. D., Stripp, B. R., & Davis, B. R. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.160 · Cited by 40
“Significantly, correction resulted in restoration of forskolininduced swelling in the puro selected organoids.(39) To establish a model for examining CFTR mutations in the hematopoietic lineage, Jennings et al.”
BackgroundMahato, R. K., Bhattacharya, S., Khullar, N., Sidhu, I. S., Reddy, P. H., Bhatti, G. K., & Bhatti, J. S. (2023) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2023.12.003 · Cited by 40
Personalized medicine for cystic fibrosis: Establishing human model systems
Mou, H., Brazauskas, K., & Rajagopal, J. (2015) · Pediatric Pulmonology · doi:10.1002/ppul.23233 · Cited by 40
“Intestinal organoids have also been used to demonstrate successful functional repair of CFTR through gene correction with the CRISPR/Cas9 system.(53) This work highlights the potential value of organoid systems in studying the effect of CFTR potentiators and correctors on an individual CF patient, as well as the effic…”
BackgroundMethodBelmadi, N., Midoux, P., Loyer, P., Passirani, C., Pichon, C., Gall, T. L., Jaffrès, P., Lehn, P., & Montier, T. (2015) · Biotechnology Journal · doi:10.1002/biot.201400841 · Cited by 46
“Indeed, correction of the CFTR locus by homologous recombination in cultured intestinal stem cells of CF patients using CRISPR/Cas9 has been successfully performed, resulting in functional expression of the corrected allele [120].”
Microfluidics platform for measurement of volume changes in immobilized intestinal enteroids
Jin, B., Battula, S. K., Zachos, N. C., Kovbasnjuk, O. N., Fawlke-Abel, J., In, J., Donowitz, M., & Verkman, A. S. (2014) · Biomicrofluidics · doi:10.1063/1.4870400 · Cited by 39
CRISPR-Cas9: A New Addition to the Drug Metabolism and Disposition Tool Box
Karlgren, M., Simoff, I., Keiser, M., Oswald, S., & Artursson, P. (2018) · Drug Metabolism and Disposition · doi:10.1124/dmd.118.082842 · Cited by 40
“In these cases, the gene edited was theCFTR gene (ABCC7) (Schwank et al., 2013) and the white gene (belonging to the ABCG family) regulating eye pigmentation in fruit fly (Kondo and Ueda, 2013), i.e., transporters not considered to be ADME proteins.”
BackgroundJosenhans, C., Müthing, J., Elling, L., Bartfeld, S., & Schmidt, H. (2020) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2020.151392 · Cited by 40
“This also allows the generation of biobanks (Van De Wetering et al., 2015) and introduction of genetic modifications such as via CRISPR/Cas9 (Schwank et al., 2013).”
BackgroundMultiplex precise base editing in cynomolgus monkeys
Zhang, W., Aida, T., del Rosario, R. C. H., Wilde, J. J., Ding, C., Zhang, X., Baloch, Z., Huang, Y., Tang, Y., Li, D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16173-0 · Cited by 42
Erwood, S., Laselva, O., Bily, T. M. I., Brewer, R. A., Rutherford, A. H., Bear, C. E., & Ivakine, E. A. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.05.002 · Cited by 40
3D organoids derived from the small intestine: An emerging tool for drug transport research
Zhang, Y., Huang, S., Zhong, W., Chen, W., Yao, B., & Wang, X. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.12.002 · Cited by 40
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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