The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
CRISPR-Based Adenine Editors Correct Nonsense Mutations in a Cystic Fibrosis Organoid Biobank
Open accessAbstract
Adenine base editing (ABE) enables enzymatic conversion from A-T into G-C base pairs. ABE holds promise for clinical application, as it does not depend on the introduction of double-strand breaks, contrary to conventional CRISPR/Cas9-mediated genome engineering. Here, we describe a cystic fibrosis (CF) intestinal organoid biobank, representing 664 patients, of which ~20% can theoretically be repaired by ABE. We apply SpCas9-ABE (PAM recognition sequence: NGG) and xCas9-ABE (PAM recognition sequence: NGN) on four selected CF organoid samples. Genetic and functional repair was obtained in all four cases, while whole-genome sequencing (WGS) of corrected lines of two patients did not detect off-target mutations. These observations exemplify the value of large, patient-derived organoid biobanks representing hereditary disease and indicate that ABE may be safely applied in human cells.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“We have previously described the use of ABEs in Cystic Fibrosis patient-derived organoids to functionally repair mutations in CFTR without genome-wide off-targets31.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [31]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“While base editors have been applied before in organoids to model36 and repair31 diseases, we significantly extend their application by demonstrating the opportunities that reside in multiplexing CBE’s and ABE’s, as well as Cas9 homologs and evolved Cas9 variants.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [31]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
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
Fast and accurate long-read alignment with Burrows-Wheeler transform.
Li, H., & Durbin, R. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp698 · Cited by 12,063
A framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,457
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210
Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage
Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A., & Liu, D. R. (2016) · Nature · doi:10.1038/nature17946 · Cited by 5,437
Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage
Gaudelli, N. M., Komor, A. C., Rees, H. A., Packer, M. S., Badran, A. H., Bryson, D. I., & Liu, D. R. (2017) · Nature · doi:10.1038/nature24644 · Cited by 4,184
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-citationHigh-Frequency off-Target Mutagenesis Induced by CRISPR-Cas Nucleases in Human Cells
Fu, Y., Foden, J. A., Khayter, C., Maeder, M. L., Reyon, D., Joung, J. K., & Sander, J. D. (2013) · Nature Biotechnology · doi:10.1038/nbt.2623 · Cited by 3,292
Sambamba: fast processing of NGS alignment formats
Tarasov, A., Vilella, A. J., Cuppen, E. P. J. G., Nijman, I. J., & Prins, P. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv098 · Cited by 2,384
Bae, S., Park, J., & Kim, J.-S. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu048 · Cited by 2,339
A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation
Ramsey, B. W., Davies, J., McElvaney, N. G., Tullis, E., Bell, S. C., Dřevínek, P., Griese, M., McKone, E. F., Wainwright, C. E., Konstan, M. W., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1105185 · Cited by 2,195
COSMIC: somatic cancer genetics at high-resolution
Forbes, S. A., Beare, D., Boutselakis, H., Bamford, S., Bindal, N., Tate, J., Cole, C. G., Ward, S., Dawson, E., Ponting, L., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1121 · Cited by 1,922
Kosicki, M., Tomberg, K., & Bradley, A. (2018) · Nature Biotechnology · doi:10.1038/nbt.4192 · Cited by 1,883
Base editing: precision chemistry on the genome and transcriptome of living cells
Rees, H. A., & Liu, D. R. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0059-1 · Cited by 1,675
Engineered CRISPR-Cas9 nucleases with altered PAM specificities
Kleinstiver, B. P., Prew, M. S., Tsai, S. Q., Topkar, V. V., Nguyen, N. T., Zheng, Z., Gonzales, A. P. W., Li, Z., Peterson, R. T., Yeh, J.-R. J., et al. (2015) · Nature · doi:10.1038/nature14592 · Cited by 1,624
Evolved Cas9 variants with broad PAM compatibility and high DNA specificity
Hu, J. H., Miller, S. M., Geurts, M. H., Tang, W., Chen, L., Sun, N., Zeina, C. M., Gao, X., Rees, H. A., Lin, Z., et al. (2018) · Nature · doi:10.1038/nature26155 · Cited by 1,552
Self-citationPattanayak, V., Lin, S., Guilinger, J. P., Ma, E., Doudna, J. A., & Liu, D. R. (2013) · Nature Biotechnology · doi:10.1038/nbt.2673 · Cited by 1,487
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., et al. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.11.002 · Cited by 1,424 · cited 2×
“Functional repair of CFTR was assessed using a forskolin-induced swelling (FIS) assay, which is impaired in CF organoids and correlates with clinical disease severity (de Winter-de Groot et al., 2018) and in vivo CFTR modulator response (Berkers et al., 2019; Dekkers et al., 2013, 2016).”
Self-citationAnalysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases
Cho, S. W., Kim, S., Kim, Y., Kweon, J., Kim, H. S., Bae, S., & Kim, J.-S. (2014) · Genome Research · doi:10.1101/gr.162339.113 · Cited by 1,356
Deciphering Signatures of Mutational Processes Operative in Human Cancer
Alexandrov, L. B., Nik‐Zainal, S., Wedge, D. C., Campbell, P. J., & Stratton, M. R. (2013) · Cell Reports · doi:10.1016/j.celrep.2012.12.008 · Cited by 1,277
Engineered CRISPR-Cas9 nuclease with expanded targeting space
Nishimasu, H., Shi, X., Ishiguro, S., Gao, L., Hirano, S., Okazaki, S., Noda, T., Abudayyeh, O. O., Gootenberg, J. S., Mori, H., et al. (2018) · Science · doi:10.1126/science.aas9129 · Cited by 1,100
Long‐term expanding human airway organoids for disease modeling
Sachs, N., Papaspyropoulos, A., Zomer‐van Ommen, D. D., Heo, I., Böttinger, L., Klay, D., Weeber, F., Huelsz‐Prince, G., Iakobachvili, N., Amatngalim, G. D., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100300 · Cited by 1,082
Self-citationA functional CFTR assay using primary cystic fibrosis intestinal organoids
Dekkers, J. F., Wiegerinck, C. L., de Jonge, H. R., Bronsveld, I., Janssens, H. M., de Winter-de Groot, K. M., Brandsma, A. M., de Jong, N. W. M., Bijvelds, M. J. C., Scholte, B. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3201 · Cited by 999
Self-citationImproving cytidine and adenine base editors by expression optimization and ancestral reconstruction
Koblan, L. W., Doman, J. L., Wilson, C., Levy, J. M., Tay, T., Newby, G. A., Maianti, J. P., Raguram, A., & Liu, D. R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4172 · Cited by 944
Tissue-specific mutation accumulation in human adult stem cells during life
Blokzijl, F., de Ligt, J., Jager, M., Sasselli, V., Roerink, S., Sasaki, N., Huch, M., Boymans, S., Kuijk, E., Prins, P., et al. (2016) · Nature · doi:10.1038/nature19768 · Cited by 935
Self-citationCytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos
Zuo, E., Sun, Y., Wei, W., Yuan, T., Ying, W., Sun, H., Yuan, L., Steinmetz, L. M., Li, Y., & Yang, H. (2019) · Science · doi:10.1126/science.aav9973 · Cited by 782
VX-445–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles
Keating, D., Marigowda, G., Burr, L., Daines, C., Mall, M. A., McKone, E. F., Ramsey, B. W., Rowe, S. M., Sass, L. A., Tullis, E., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1807120 · Cited by 726
Self-citationCytosine, but not adenine, base editors induce genome-wide off-target mutations in rice
Jin, S., Zong, Y., Gao, Q., Zhu, Z., Wang, Y., Qin, P., Liang, C., Wang, D., Qiu, J.-L., Zhang, F., et al. (2019) · Science · doi:10.1126/science.aaw7166 · Cited by 665
MutationalPatterns: comprehensive genome-wide analysis of mutational processes
Blokzijl, F., Janssen, R., van Boxtel, R., & Cuppen, E. (2018) · Genome Medicine · doi:10.1186/s13073-018-0539-0 · Cited by 660
Sosnay, P. R., Siklosi, K. R., Van Goor, F., Kaniecki, K., Yu, H., Sharma, N., Ramalho, A. S., Amaral, M. D., Dorfman, R., Zielenski, J., et al. (2013) · Nature Genetics · doi:10.1038/ng.2745 · Cited by 630
Dekkers, J. F., Berkers, G., Kruisselbrink, E., Vonk, A., de Jonge, H. R., Janssens, H. M., Bronsveld, I., van de Graaf, E. A., Nieuwenhuis, E. E. S., Houwen, R. H. J., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad8278 · Cited by 548
Self-citationDual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells
Mou, H., Vinarsky, V., Tata, P. R., Brazauskas, K., Choi, S. H., Crooke, A. K., Zhang, B., Solomon, G. M., Turner, B., Bihler, H. J., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.05.012 · Cited by 387
Efficient genetic engineering of human intestinal organoids using electroporation
Fujii, M., Matano, M., Nanki, K., & Sato, T. (2015) · Nature Protocols · doi:10.1038/nprot.2015.088 · Cited by 364
Optimized base editors enable efficient editing in cells, organoids and mice
Zafra, M. P., Schatoff, E. M., Katti, A., Foronda, M., Breinig, M., Schweitzer, A. Y., Simon, A., Han, T., Goswami, S., Montgomery, E., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4194 · Cited by 347
Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis
Berkers, G., van Mourik, P., Vonk, A. M., Kruisselbrink, E., Dekkers, J. F., de Winter-de Groot, K. M., Arets, H. G. M., Marck-van der Wilt, R. E. P., Dijkema, J. S., Vanderschuren, M. M., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.068 · Cited by 310
Self-citationImproving Plant Genome Editing with High-Fidelity xCas9 and Non-canonical PAM-Targeting Cas9-NG
Zhong, Z., Sretenovic, S., Ren, Q., Yang, L., Bao, Y., Qi, C., Yuan, M., He, Y., Liu, S., Liu, X., et al. (2019) · Molecular Plant · doi:10.1016/j.molp.2019.03.011 · Cited by 201
Rational Development of Addiction Pharmacotherapies: Successes, Failures, and ProspectsPreprint
Pierce, R. C., O'Brien, C. P., Kenny, P. J., & Vanderschuren, L. J. M. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a012880 · Cited by 178
Boj, S. F., Vonk, A. M., Statia, M., Su, J., Dekkers, J. F., Vries, R., Beekman, J. M., & Clevers, H. C. (2017) · Journal of Visualized Experiments · doi:10.3791/55159 · Cited by 138
Self-citationAssessing the Disease-Liability of Mutations in CFTRPreprint
Férec, C., & Cutting, G. R. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009480 · Cited by 107
Green, D. M., McDougal, K. E., Blackman, S. M., Sosnay, P. R., Henderson, L. B., Naughton, K., Collaco, J. M., & Cutting, G. R. (2010) · Respiratory Research · doi:10.1186/1465-9921-11-140 · Cited by 88
One-step generation of conditional and reversible gene knockouts
Andersson-Rolf, A., Mustata, R. C., Merenda, A., Kim, J., Perera, S., Grego, T., Andrews, K., Tremble, K., Silva, J., Fink, J., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4156 · Cited by 83
Groot, K. M. D. W., Janssens, H. M., van Uum, R. T., Dekkers, J. F., Berkers, G., Vonk, A. M., Kruisselbrink, E., Oppelaar, H., Vries, R. G. J., Clevers, H. C., et al. (2018) · European Respiratory Journal · doi:10.1183/13993003.02529-2017 · Cited by 80
Self-citationJager, M., Blokzijl, F., Sasselli, V., Boymans, S., Janssen, R., Besselink, N., Clevers, H., van Boxtel, R., & Cuppen, E. (2018) · Nature Protocols · doi:10.1038/nprot.2017.111 · Cited by 66
Self-citation
Flagged first, then by citations
1 of the 46 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Establishment of patient-derived cancer organoids for drug-screening applications
Driehuis, E., Kretzschmar, K., & Clevers, H. C. (2020) · Nature Protocols · doi:10.1038/s41596-020-0379-4 · Cited by 685
Self-citationHuman organoids in basic research and clinical applications
Tang, X.-Y., Wu, S., Wang, D., Chu, C., Hong, Y., Tao, M., Hu, H., Xu, M., Guo, X. L., & Liu, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01024-9 · Cited by 539
Organoids: The current status and biomedical applications
Yang, S., Hu, H., Kung, H., Zou, R.-Q., Dai, Y.-S., Hu, Y.-F., Wang, T., Lv, T., Yu, J., & Li, F. (2023) · MedComm · doi:10.1002/mco2.274 · Cited by 300
Establishment and Culture of Human Intestinal Organoids Derived from Adult Stem Cells
Pleguezuelos‐Manzano, C., Puschhof, J., van den Brink, S., Geurts, V., Beumer, J., & Clevers, H. C. (2020) · Current Protocols in Immunology · doi:10.1002/cpim.106 · Cited by 271
Self-citationBioengineering Approaches for the Advanced Organoid Research
Yi, S. A., Zhang, Y., Rathnam, C., Pongkulapa, T., & Lee, K. (2021) · Advanced Materials · doi:10.1002/adma.202007949 · Cited by 218
Metadata
- Authors
- Geurts, M. H., de Poel, E., Amatngalim, G. D., Oka, R., Meijers, F. M., Kruisselbrink, E., van Mourik, P., Berkers, G., de Winter-de Groot, K. M., Michel, S., Muilwijk, D., Aalbers, B. L., Mullenders, J., Boj, S. F., Suen, S. W. F., Brunsveld, J. E., Janssens, H. M., Mall, M. A., Graeber, S. Y., van Boxtel, R., van der Ent, C. K., Beekman, J. M., & Clevers, H.
- Affiliations
- Royal Netherlands Academy of Arts and Sciences (NL)
- Utrecht University (NL)
- Oncode Institute (NL)
- Erasmus MC (NL)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Corresponding author
- Beekman, Jeffrey M.
- Clevers, Hans
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 26
- Issue
- 4
- Pages
- 503-510.e7
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W3007694991
- Cited by
- 222
- References
- 46
- Citations by year
- 2026: 19 · 2025: 33 · 2024: 31 · 2023: 37 · 2022: 33 · 2021: 44 · 2020: 25
- FWCI
- 11.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Funders
- Cancer Research UK (C6307/A29058)
- Charité – Universitätsmedizin Berlin
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (737.016.009)
- Berlin Institute of Health
- Nederlandse Cystic Fibrosis Stichting
- 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 › Molecular Biology › RNA regulation and disease
- Keywords
- adenine base editing, cystic fibrosis, nonsense mutation, intestinal organoids, organoid biobank, gene correction, off-target mutations, genetic disorders, patient-derived cells
- MeSH terms
- Gene Editing, CRISPR-Associated Protein 9, Adenine, Cystic Fibrosis, Humans, Organoids, Biological Specimen Banks, Codon, Nonsense, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
