rAAV-CFTRΔR Rescues the Cystic Fibrosis Phenotype in Human Intestinal Organoids and Cystic Fibrosis Mice
Open accessAbstract
Rationale: Gene therapy holds promise for a curative mutation-independent treatment applicable to all patients with cystic fibrosis (CF). The various viral vector–based clinical trials conducted in the past have demonstrated safety and tolerance of different vectors, but none have led to a clear and persistent clinical benefit. Recent clinical breakthroughs in recombinant adeno-associated viral vector (rAAV)-based gene therapy encouraged us to reexplore an rAAV approach for CF. Objectives: We evaluated the preclinical potential of rAAV gene therapy for CF to restore chloride and fluid secretion in two complementary models: intestinal organoids derived from subjects with CF and a CF mouse model, an important milestone toward the development of a clinical rAAV candidate for CF gene therapy. Methods: We engineered an rAAV vector containing a truncated CF transmembrane conductance regulator (CFTRΔR) combined with a short promoter (CMV173) to ensure optimal gene expression. A rescue in chloride and fluid secretion after rAAV-CFTRΔR treatment was assessed by forskolin-induced swelling in CF transmembrane conductance regulator (CFTR)-deficient organoids and by nasal potential differences in ΔF508 mice. Measurements and Main Results: rAAV-CFTRΔR transduction of human CFTR-deficient organoids resulted in forskolin-induced swelling, indicating a restoration of CFTR function. Nasal potential differences demonstrated a clear response to low chloride and forskolin perfusion in most rAAV-CFTRΔR-treated CF mice. Conclusions: Our study provides robust evidence that rAAV-mediated gene transfer of a truncated CFTR functionally rescues the CF phenotype across the nasal mucosa of CF mice and in patient-derived organoids. These results underscore the clinical potential of rAAV-CFTRΔR in offering a cure for all patients with CF in the future.
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
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?
Viral and non-viral vectors have proven valid to deliver the CFTR cDNA in cell and animal models of CF.
“Viral and non-viral vectors have proven valid to deliver the CFTR cDNA in cell and animal models of CF8,10.”
From Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing (2019) · cites this paper as [8]
The Discussion (p. 7) reports that viral rAAV delivery of truncated CFTR improved channel activity in human intestinal organoids and CF mice, supporting the cell- and animal-model part of the claim. It discusses nonviral liposome delivery of CFTR cDNA in patients, not in those models; the paper's own vector also carries a truncated CFTR sequence rather than full-length CFTR cDNA. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · see citing works
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 · see citing works
Self-citationNon-viral vectors for gene-based therapy
Yin, H., Kanasty, R. L., Eltoukhy, A. A., Vegas, A. J., Dorkin, J. R., & Anderson, D. G. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3763 · Cited by 3,123 · see citing works
Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
Sato, T., van Es, J. H., Snippert, H. J., Stange, D. E., Vries, R. G., van den Born, M., Barker, N., Shroyer, N. F., van de Wetering, M., & Clevers, H. (2011) · Nature · doi:10.1038/nature09637 · Cited by 2,510 · see citing works
Manno, C. S., Pierce, G. F., Arruda, V. R., Glader, B., Ragni, M., Rasko, J. J. E., Ozelo, M. C., Hoots, K., Blatt, P., Konkle, B., et al. (2006) · Nature Medicine · doi:10.1038/nm1358 · Cited by 2,163 · see citing works
Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B
Nathwani, A. C., Tuddenham, E. G. D., Rangarajan, S., Rosales, C., McIntosh, J., Linch, D. C., Chowdary, P., Riddell, A., Pie, A. J., Harrington, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1108046 · Cited by 1,864 · see citing works
Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del <i>CFTR</i>
Wainwright, C. E., Elborn, J. S., Ramsey, B. W., Marigowda, G., Huang, X., Cipolli, M., Colombo, C., Davies, J. C., De Boeck, K., Flume, P. A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1409547 · Cited by 1,622 · see citing works
Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B
Nathwani, A. C., Reiss, U. M., Tuddenham, E. G. D., Rosales, C., Chowdary, P., McIntosh, J., Della Peruta, M., Lheriteau, E., Patel, N., Raj, D., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1407309 · Cited by 1,273 · see citing works
A 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 · see citing works
Self-citationBoutin, S., Monteilhet, V., Veron, P., Leborgne, C., Benveniste, O., Montus, M. F., & Masurier, C. (2010) · Human Gene Therapy · doi:10.1089/hum.2009.182 · Cited by 970 · see citing works
Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses
Calcedo, R., Vandenberghe, L. H., Gao, G., Lin, J., & Wilson, J. M. (2009) · The Journal of Infectious Diseases · doi:10.1086/595830 · Cited by 808 · see citing works
Disruption of the CFTR Gene Produces a Model of Cystic Fibrosis in Newborn Pigs
Rogers, C. S., Stoltz, D. A., Meyerholz, D. K., Ostedgaard, L. S., Rokhlina, T., Taft, P. J., Rogan, M. P., Pezzulo, A. A., Karp, P. H., Itani, O. A., et al. (2008) · Science · doi:10.1126/science.1163600 · Cited by 752 · see citing works
Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling
Rock, J. R., Randell, S. H., & Hogan, B. L. M. (2010) · Disease Models & Mechanisms · doi:10.1242/dmm.006031 · Cited by 724 · see citing works
Isolation and in vitro expansion of human colonic stem cells
Jung, P., Sato, T., Merlos-Suárez, A., Barriga, F. M., Iglesias, M., Rossell, D., Auer, H., Gallardo, M., Blasco, M. A., Sancho, E., et al. (2011) · Nature Medicine · doi:10.1038/nm.2470 · Cited by 709 · see citing works
Zabner, J., Couture, L., Gregory, R., Graham, S., Smith, A. E., & Welsh, M. (1993) · Cell · doi:10.1016/0092-8674(93)80063-k · Cited by 657 · see citing works
Dystrophin Immunity in Duchenne's Muscular Dystrophy
Mendell, J. R., Campbell, K., Rodino-Klapac, L., Sahenk, Z., Shilling, C., Lewis, S., Bowles, D., Gray, S., Li, C., Galloway, G., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1000228 · Cited by 655 · see citing works
Alton, E. W. F. W., Armstrong, D. K., Ashby, D., Bayfield, K. J., Bilton, D., Bloomfield, E. V., Boyd, A. C., Brand, J., Buchan, R., Calcedo, R., et al. (2015) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(15)00245-3 · Cited by 428 · see citing works
Pathophysiology of Gene-Targeted Mouse Models for Cystic Fibrosis
Grubb, B. R., & Boucher, R. C. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.1.s193 · Cited by 411 · see citing works
Moss, R. B., Rodman, D. M., Spencer, L. T., Aitken, M. L., Zeitlin, P. L., Waltz, D. A., Milla, C. E., Brody, A. S., Clancy, J. P., Ramsey, B. W., et al. (2004) · CHEST Journal · doi:10.1378/chest.125.2.509 · Cited by 389 · see citing works
Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis
Sun, X., Sui, H., Fisher, J. T., Yan, Z., Liu, X., Cho, H., Joo, N. S., Zhang, Y., Zhou, W., Yi, Y., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43052 · Cited by 370 · see citing works
Overcoming Preexisting Humoral Immunity to AAV Using Capsid Decoys
Mingozzi, F., Anguela, X. M., Pavani, G., Chen, Y., Davidson, R. J., Hui, D. J., Yazicioglu, M., Elkouby, L., Hinderer, C. J., Faella, A., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005795 · Cited by 355 · see citing works
Grimm, D., & Kay, M. A. (2003) · Current Gene Therapy · doi:10.2174/1566523034578285 · Cited by 349 · see citing works
Zabner, J., Seiler, M. P., Walters, R. H., Kotin, R., Fulgeras, W., Davidson, B., & Chiorini, J. (2000) · Journal of Virology · doi:10.1128/jvi.74.8.3852-3858.2000 · Cited by 329 · see citing works
In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector
Zinn, E., Pacouret, S., Khaychuk, V., Turunen, H. T., Carvalho, L. S., Andres-Mateos, E., Shah, S., Shelke, R., Maurer, A. C., Plovie, E., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.019 · Cited by 310 · see citing works
Ciliated epithelial cell lifespan in the mouse trachea and lung
Rawlins, E. L., & Hogan, B. L. M. (2008) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.90209.2008 · Cited by 304 · see citing works
Sheridan, C. (2011) · Nature Biotechnology · doi:10.1038/nbt.1769 · Cited by 302 · see citing works
Moss, R. B., Milla, C. E., Colombo, J. L., Accurso, F. J., Zeitlin, P. L., Clancy, J. P., Spencer, L. T., Pilewski, J. M., Waltz, D. A., Dorkin, H. L., et al. (2007) · Human Gene Therapy · doi:10.1089/hum.2007.022 · Cited by 276 · see citing works
Halbert, C. L., Rutledge, E. A., Allen, J. M., Russell, D. W., & Miller, A. D. (2000) · Journal of Virology · doi:10.1128/jvi.74.3.1524-1532.2000 · Cited by 259 · see citing works
A mouse model for the cystic fibrosis delta F508 mutation.
van Doorninck, J. H., French, P. J., Verbeek, E., Peters, R. H., Morreau, H., Bijman, J., & Scholte, B. J. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00119.x · Cited by 245 · see citing works
Flotte, T. R., Zeitlin, P. L., Reynolds, T. C., Heald, A. E., Pedersen, P. S., Beck, S. E., Conrad, C., Brass‐Ernst, L., Humphries, M. R., Sullivan, K., et al. (2003) · Human Gene Therapy · doi:10.1089/104303403322124792 · Cited by 244 · see citing works
Halbert, C. L., Standaert, T. A., Wilson, C. B., & Miller, A. D. (1998) · Journal of Virology · doi:10.1128/jvi.72.12.9795-9805.1998 · Cited by 203 · see citing works
Mouse models of cystic fibrosis: Phenotypic analysis and research applications
Wilke, M., Buijs‐Offerman, R. M., Aarbiou, J., Colledge, W. H., Sheppard, D. N., Touqui, L., Bot, A. G. M., Jorna, H., de Jonge, H. R., & Scholte, B. J. (2011) · Journal of Cystic Fibrosis · doi:10.1016/s1569-1993(11)60020-9 · Cited by 200 · see citing works
Duan, D., Yue, Y., Yan, Z., McCray, P. B., & Engelhardt, J. F. (1998) · Human Gene Therapy · doi:10.1089/hum.1998.9.18-2761 · Cited by 171 · see citing works
Lock, M., Alvira, M. R., Chen, S.-J., & Wilson, J. M. (2014) · Human Gene Therapy Methods · doi:10.1089/hgtb.2013.131 · Cited by 163 · see citing works
Tuggle, K. L., Birket, S. E., Cui, X., Hong, J. S., Warren, J., Reid, L., Chambers, A., Ji, D., Gamber, K. M., Chu, K. K., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091253 · Cited by 159 · see citing works
Upscaling of lentiviral vector production by tangential flow filtration
Geraerts, M., Michiels, M., Baekelandt, V., Debyser, Z., & Gijsbers, R. (2005) · The Journal of Gene Medicine · doi:10.1002/jgm.778 · Cited by 158 · see citing works
Self-citationLimberis, M. P., & Wilson, J. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601433103 · Cited by 154 · see citing works
Noninvasive gene transfer to the lung for systemic delivery of therapeutic proteins
Auricchio, A., O’Connor, E., Weiner, D. J., Gao, G., Hildinger, M., Wang, L., Calcedo, R., & Wilson, J. M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15780 · Cited by 150 · see citing works
Mingozzi, F., Chen, Y., Edmonson, S. C., Zhou, S., Thurlings, R. M., Tak, P. P., High, K. A., & Vervoordeldonk, M. J. (2013) · Gene Therapy · doi:10.1038/gt.2012.55 · Cited by 138 · see citing works
Farmen, S. L., Karp, P. H., Ng, P., Palmer, D. J., Koehler, D. R., Hu, J., Beaudet, A. L., Zabner, J., & Welsh, M. J. (2005) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00049.2005 · Cited by 138 · see citing works
Toward Gene Therapy for Cystic Fibrosis Using a Lentivirus Pseudotyped With Sendai Virus Envelopes
Mitomo, K., Uta Griesenbach, D., Inoue, M., Somerton, L., Meng, C., Akiba, E., Tabata, T., Ueda, Y., Frankel, G. M., Farley, R., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.13 · Cited by 135 · see citing works
New clinical diagnostic procedures for cystic fibrosis in Europe
Boeck, K. D., Derichs, N., Fajac, I., de Jonge, H. R., Bronsveld, I., Sermet‐Gaudelus, I., Vermeulen, F. L., Sheppard, D. N., Cuppens, H., Hug, M., et al. (2011) · Journal of Cystic Fibrosis · doi:10.1016/s1569-1993(11)60009-x · Cited by 124 · see citing works
Self-citationSinn, P. L., Burnight, E. R., Hickey, M. A., Blissard, G. W., & McCray, P. B. (2005) · Journal of Virology · doi:10.1128/jvi.79.20.12818-12827.2005 · Cited by 113 · see citing works
CFTR biomarkers: time for promotion to surrogate end-point
Boeck, K. D., Kent, L., Davies, J. C., Derichs, N., Amaral, M. D., Rowe, S. M., Middleton, P. G., de Jonge, H. R., Bronsveld, I., Wilschanski, M. A., et al. (2012) · European Respiratory Journal · doi:10.1183/09031936.00057512 · Cited by 109 · see citing works
Self-citationAssessment of F/HN-Pseudotyped Lentivirus as a Clinically Relevant Vector for Lung Gene Therapy
Uta Griesenbach, D., Inoue, M., Meng, C., Farley, R., Chan, M., Newman, N. K., Brum, A. M., You, J., Kerton, A., Shoemark, A., et al. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201206-1056oc · Cited by 108 · see citing works
Novel personalized therapies for cystic fibrosis: treating the basic defect in all patients
Amaral, M. D. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12314 · Cited by 107 · see citing works
Ostedgaard, L. S., Rokhlina, T., Karp, P. H., Lashmit, P., Afione, S., Schmidt, M., Zabner, J., Stinski, M. F., Chiorini, J. A., & Welsh, M. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409845102 · Cited by 105 · see citing works
Sequential targeting of CFTR by BAC vectors generates a novel pig model of cystic fibrosis
Klymiuk, N., Mundhenk, L., Kraehe, K., Wuensch, A., Plog, S., Emrich, D., Langenmayer, M. C., Stehr, M., Holzinger, A., Kröner, C., et al. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0839-y · Cited by 100 · see citing works
Novel opportunities for CFTR-targeting drug development using organoids
Dekkers, J. F., van der Ent, C. K., & Beekman, J. M. (2013) · Rare Diseases · doi:10.4161/rdis.27112 · Cited by 93 · see citing works
Self-citationKelly, M., Trudel, S., Brouillard, F., Bouillaud, F., Colas, J., Nguyen‐Khoa, T., Ollero, M., Edelman, A., & Fritsch, J. (2010) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.162032 · Cited by 86 · see citing works
Self-citationDiscovery of novel potent ΔF508‐CFTR correctors that target the nucleotide binding domain
Odolczyk, N., Fritsch, J., Norez, C., Servel, N., da Cunha, M. F., Bitam, S., Kupniewska, A., Wiszniewski, L., Colas, J., Tarnowski, K., et al. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201302699 · Cited by 86 · see citing works
Self-citationBiosafety of recombinant adeno-associated virus vectors.
Dismuke, D., Tenenbaum, L., & Samulski, R. (2014) · Current Gene Therapy · doi:10.2174/15665232113136660007 · Cited by 83 · see citing works
Moving forward: cystic fibrosis gene therapy
Uta Griesenbach, D., & Alton, E. W. F. W. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt372 · Cited by 76 · see citing works
Sermet‐Gaudelus, I., Girodon, E., Sands, D., Stremmler, N., Vávrová, V., Deneuville, E., Reix, P., Bui, S., Huet, F., Bourgeois, M. L., et al. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201003-0382oc · Cited by 71 · see citing works
Self-citationOstedgaard, L. S., Zabner, J., Vermeer, D. W., Rokhlina, T., Karp, P. H., Stecenko, A. A., Randak, C. O., & Welsh, M. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261714599 · Cited by 61 · see citing works
Dual Reporter Comparative Indexing of rAAV Pseudotyped Vectors in Chimpanzee Airway
Flotte, T. R., Fischer, A. C., Goetzmann, J. E., Mueller, C., Cebotaru, L., Yan, Z., Wang, L., Wilson, J. M., Guggino, W. B., & Engelhardt, J. F. (2009) · Molecular Therapy · doi:10.1038/mt.2009.230 · Cited by 56 · see citing works
Association between Hsp90 and the ClC-2 chloride channel upregulates channel function.
Hinzpeter, A., Lipecka, J., Brouillard, F., Baudoin-Legros, M., Dadlez, M., Edelman, A., & Fritsch, J. (2006) · American Journal of Physiology - Cell Physiology · doi:10.1152/ajpcell.00209.2005 · Cited by 51 · see citing works
Self-citationVaandrager, A. B., Bajnath, R. B., Groot, J. A., Bot, A. G. M., & de Jonge, H. R. (1991) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1991.261.6.g958 · Cited by 41 · see citing works
Long-term persistence of gene expression from adeno-associated virus serotype 5 in the mouse airways
Jones, S., Davies, L. A., Varathalingam, A., Gill, D. R., & Hyde, S. C. (2006) · Gene Therapy · doi:10.1038/sj.gt.3302815 · Cited by 36 · see citing works
Efficient Gene Transfer Into the Mouse Lung by Fetal Intratracheal Injection of rAAV2/6.2
Carlon, M. S., Toelen, J., der Perren, A. V., Vandenberghe, L. H., Reumers, V., Sbragia, L., Gijsbers, R., Baekelandt, V., Himmelreich, U., Wilson, J. M., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.153 · Cited by 35 · see citing works
Self-citationCebotaru, L., Vij, N., Ciobanu, I., Wright, J., Flotte, T. R., & Guggino, W. B. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709156200 · Cited by 34 · see citing works
Cebotaru, L., Woodward, O. M., Cebotaru, V., & Guggino, W. B. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.420489 · Cited by 20 · see citing works
Carlon, M. S., Vidović, D., Dooley, J., da Cunha, M. M., Maris, M., Lampi, Y., Toelen, J., Van den Haute, C., Baekelandt, V., Deprest, J., et al. (2014) · Human Gene Therapy · doi:10.1089/hum.2013.196 · Cited by 19 · see citing works
Self-citationNivsarkar, M. S., Buckley, S. M. K., Parker, A. L., Perocheau, D. P. B., McKay, T. R., Rahim, A. A., Howe, S. J., & Waddington, S. N. (2015) · Journal of Immunology Research · doi:10.1155/2015/397879 · Cited by 15 · see citing works
Characterization of Nasal Potential Difference in cftr Knockout and F508del-CFTR Mice
Saussereau, E., Roussel, D., Diallo, S., Debarbieux, L., Edelman, A., & Sermet‐Gaudelus, I. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057317 · Cited by 15 · see citing works
Self-citationIntersection of Gene Therapy and Progenitor Cell Biology in the Lung
Weiss, D. J. (2009) · Molecular Therapy · doi:10.1038/mt.2008.285 · Cited by 3 · see citing works
Carlon, M. S., Vidović, D., Dekkers, J. F., da Cunha, M. F., Hollenhorst, M. I., Bijvelds, M. J. C., den Haute, C. V., Baekelandt, V., de Jonge, H. R., Boeck, K. D., et al. (2015) · Journal of Cystic Fibrosis · doi:10.1016/s1569-1993(15)30001-1 · Cited by 2 · see citing works
Self-citation
Flagged first, then by citations
1 of the 68 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- [9]9. Moss RB, Milla C, Colombo J, Accurso F, Zeitlin PL, Clancy JP, Spencer LT, Pilewski J, Waltz DA, Dorkin HL, et al . Repeated aerosolized AAVCFTR for treatment of cystic fi brosis: a randomized placebocontrolled phase 2B trial. Hum Gene Ther 2007;18:726 -732.
- [21]21. Vidovic D, Carlon M, da Cunha MF, Dekkers J, Hollenhorst M, Bijvelds M, Van den Haute C, Baekelandt V, de Jonge H, Beekman J, et al . rAAV2/5 encoding truncated CFTR corrects CF phenotype in mouse nasal epithelium [abstract]. Hum Gene Ther 2014;25: A115 -A116.
- [22]22. Vidovic D, Carlon M, Faria da Cunha M, Dekkers J, Hollenhorst M, Bijvelds M, Van den Haute C, Baekelandt V, de Jonge H, SermetGaudelus I, et al . rAAV2/5 encoding truncated CFTR rescues CF phenotype in D F508 mouse model [abstract]. Presented at the 12th ECFS Basic Science Conference. March 25 -28, 2015, Algarve, Portugal. Poster 15.
Cited by
Sorted by citations
Tumor Organoids as a Pre-clinical Cancer Model for Drug Discovery
Weeber, F., Ooft, S., Dijkstra, K. K., & Voest, E. E. (2017) · Cell chemical biology · doi:10.1016/j.chembiol.2017.06.012 · Cited by 486 · see citing works
Cystic fibrosis: a clinical view
Castellani, C., & Assael, B. M. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2393-9 · Cited by 255 · see citing works
In vivo editing of lung stem cells for durable gene correction in mice
Sun, Y., Chatterjee, S., Lian, X., Traylor, Z., Sattiraju, S. R., Xiao, Y., Dilliard, S. A., Sung, Y., Kim, M., Lee, S. M., et al. (2024) · Science · doi:10.1126/science.adk9428 · Cited by 185 · see citing works
Gut organoids: mini-tissues in culture to study intestinal physiology and disease
Almeqdadi, M., Mana, M., Roper, J., & Yilmaz, Ö. H. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00300.2017 · Cited by 151 · see citing works
Research Progress, Challenges, and Breakthroughs of Organoids as Disease Models
Huang, Y., Huang, Z., Tang, Z., Chen, Y., Huang, M., Liu, H., Huang, W., Ye, Q., & Jia, B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.740574 · Cited by 128 · see citing works
Emerging Therapeutic Approaches for Cystic Fibrosis. From Gene Editing to Personalized Medicine
Pranke, I. M., Golec, A., Hinzpeter, A., Edelman, A., & Sermet‐Gaudelus, I. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00121 · Cited by 121 · see citing works
Self-citationAnimal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences
Lavelle, G., White, M. M., Browne, N., McElvaney, N. G., & Reeves, E. P. (2016) · BioMed Research International · doi:10.1155/2016/5258727 · Cited by 104 · see citing works
Verstegen, M. M. A., Roos, F. J. M., Burka, K., Gehart, H., Jager, M., de Wolf, M., Bijvelds, M. J. C., de Jonge, H. R., Ardisasmita, A. I., van Huizen, N. A., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-79082-8 · Cited by 86 · see citing works
Self-citationAllele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing
Maule, G., Casini, A., Montagna, C., Ramalho, A. S., De Boeck, K., Debyser, Z., Carlon, M. S., Petris, G., & Cereseto, A. (2019) · Nature Communications · doi:10.1038/s41467-019-11454-9 · Cited by 86 · see citing works
Self-citationRevolutionizing immune research with organoid-based co-culture and chip systems
Papp, D., Korcsmáros, T., & Hautefort, I. (2024) · Clinical & Experimental Immunology · doi:10.1093/cei/uxae004 · Cited by 73 · see citing works
Bulcaen, M., Kortleven, P., Liu, R. B., Maule, G., Dreano, E., Kelly, M., Ensinck, M. M., Thierie, S., Smits, M., Ciciani, M., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101544 · Cited by 69 · see citing works
Self-citationDelivery of genome-editing biomacromolecules for treatment of lung genetic disorders
Wan, T. Y., & Yuan, P. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.05.002 · Cited by 55 · see citing works
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 50 · see citing works
Assays of CFTR Function In Vitro, Ex Vivo and In Vivo
Ramalho, A. S., Boon, M., Proesmans, M., Vermeulen, F. L., Carlon, M. S., & Boeck, K. D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031437 · Cited by 47 · see citing works
Self-citationEmerging 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 · see citing works
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 39 · see citing works
Genetic therapies for cystic fibrosis lung disease
Hart, S. L., & Harrison, P. T. (2017) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2017.10.006 · Cited by 37 · see citing works
Genetic Modification of the Lung Directed Toward Treatment of Human Disease
Sondhi, D., Stiles, K. M., De, B. P., & Crystal, R. G. (2017) · Human Gene Therapy · doi:10.1089/hum.2016.152 · Cited by 36 · see citing works
Functional Consequences of CFTR Interactions in Cystic Fibrosis
Ramananda, Y., Naren, A. P., & Arora, K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063384 · Cited by 36 · see citing works
Dzobo, K., Rowe, A., Senthebane, D. A., AlMazyadi, M., Patten, V. A., & Parker, M. I. (2018) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2018.0172 · Cited by 36 · see citing works
Organoids: Past Learning and Future Directions
O’Connell, L., & Winter, D. C. (2019) · Stem Cells and Development · doi:10.1089/scd.2019.0227 · Cited by 36 · see citing works
Individualized medicine using intestinal responses to CFTR potentiators and correctors
Beekman, J. M. (2016) · Pediatric Pulmonology · doi:10.1002/ppul.23553 · Cited by 36 · see citing works
Self-citationPhenotyping of Rare CFTR Mutations Reveals Distinct Trafficking and Functional Defects
Ensinck, M. M., Keersmaecker, L. D., Heylen, L., Ramalho, A. S., Gijsbers, R., Farré, R., Boeck, K. D., Christ, F., Debyser, Z., & Carlon, M. S. (2020) · Cells · doi:10.3390/cells9030754 · Cited by 34 · see citing works
Self-citationSchneider‐Futschik, E. K. (2019) · Gene Therapy · doi:10.1038/s41434-019-0092-5 · Cited by 34 · see citing works
Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy
Bandara, R. A., Chen, Z. R., & Hu, J. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00662-w · Cited by 34 · see citing works
Cystic fibrosis: new challenges and perspectives beyond elexacaftor/tezacaftor/ivacaftor
Terlizzi, V., & Lopes‐Pacheco, M. (2025) · Therapeutic Advances in Respiratory Disease · doi:10.1177/17534666251323194 · Cited by 34 · see citing works
Gene therapy for Cystic Fibrosis: recent advances and future prospects
Lomunova, M. A., & Михайлович, Г. П. (2023) · Acta Naturae · doi:10.32607/actanaturae.11708 · Cited by 35 · see citing works
Organoids and microphysiological systems: Promising models for accelerating AAV gene therapy studies
Ramamurthy, R. M., Atala, A., Porada, C. D., & Almeida-Porada, G. D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1011143 · Cited by 33 · see citing works
One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies
Ensinck, M. M., & Carlon, M. S. (2022) · Cells · doi:10.3390/cells11121868 · Cited by 31 · see citing works
Self-citationOn the Corner of Models and Cure: Gene Editing in Cystic Fibrosis
Ensinck, M. M., Mottais, A., Detry, C., Leal, T., & Carlon, M. S. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.662110 · Cited by 28 · see citing works
Self-citationIshibashi, Y., Sung, C. Y. W., Grati, M., & Chien, W. W. (2023) · Hearing Research · doi:10.1016/j.heares.2023.108735 · Cited by 27 · see citing works
Ai, J., Li, J., Gessler, D. J., Su, Q., Wei, Q., Li, H., & Gao, G. (2017) · Scientific Reports · doi:10.1038/srep40336 · Cited by 26 · see citing works
Nanoblades allow high-level genome editing in murine and human organoids
Tiroille, V., Krug, A., Bokobza, E., Kahi, M., Bulcaen, M., Ensinck, M. M., Geurts, M. H., Hendriks, D., Vermeulen, F., Larbret, F., et al. (2023) · Molecular Therapy - Nucleic Acids · doi:10.1016/j.omtn.2023.06.004 · Cited by 25 · see citing works
Self-citationCurrent AAV-mediated gene therapy in sensorineural hearing loss
Qi, J., Fu, X., Zhang, L., Tan, F., Li, N., Sun, Q., Hu, X., He, Z., Xia, M., & Chai, R. (2022) · Fundamental Research · doi:10.1016/j.fmre.2022.08.015 · Cited by 24 · see citing works
Pharmacological analysis of CFTR variants of cystic fibrosis using stem cell-derived organoids
Chen, K. G., Zhong, P., Zheng, W., & Beekman, J. M. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.05.029 · Cited by 24 · see citing works
Self-citationStem cell‐derived organoids to model gastrointestinal facets of cystic fibrosis
Hohwieler, M., Perkhofer, L., Liebau, S., Seufferlein, T. T. W., Müller, M., Illing, A., & Kleger, A. (2016) · United European Gastroenterology Journal · doi:10.1177/2050640616670565 · Cited by 23 · see citing works
Patrício, D., Santiago, J., Mano, J. F., & Fardilha, M. (2022) · WIREs Mechanisms of Disease · doi:10.1002/wsbm.1590 · Cited by 23 · see citing works
The revolution of personalized pharmacotherapies for cystic fibrosis: what does the future hold?
Oliver, K. E., Carlon, M. S., Pedemonte, N., & Lopes‐Pacheco, M. (2023) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2023.2230129 · Cited by 18 · see citing works
Self-citationCritical role of TPRN rings in the stereocilia for hearing
Qi, J., Tan, F., Zhang, L., Zhou, Y., Zhang, Z., Sun, Q., Li, N., Fang, Y., Chen, X., Wu, Y., et al. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.11.011 · Cited by 16 · see citing works
Roadmap for an early gene therapy for cystic fibrosis airway disease
Carlon, M. S., Vidović, D., & Birket, S. E. (2017) · Prenatal Diagnosis · doi:10.1002/pd.5164 · Cited by 16 · see citing works
Self-citationRewriting CFTR to cure cystic fibrosis
Maule, G., Ensinck, M. M., Bulcaen, M., & Carlon, M. S. (2021) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.12.018 · Cited by 16 · see citing works
Self-citationAdvances in the Cystic Fibrosis Drug Development Pipeline
Esposito, C. T., Kämper, M., Trentacoste, J., Galvin, S., Pfister, H., & Wang, J. (2023) · Life · doi:10.3390/life13091835 · Cited by 14 · see citing works
Buckinx, R., & Timmermans, J. (2016) · Histochemistry and Cell Biology · doi:10.1007/s00418-016-1496-6 · Cited by 14 · see citing works
Using 3D Organoid Cultures to Model Intestinal Physiology and Colorectal Cancer
Short, S. P., Costacurta, P. W., & Williams, C. S. (2017) · Current Colorectal Cancer Reports · doi:10.1007/s11888-017-0363-8 · Cited by 13 · see citing works
Anticipating New Treatments for Cystic Fibrosis: A Global Survey of Researchers
Cabral, B. P., Terlizzi, V., Laselva, O., Filho, C. G. C., & Mota, F. B. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11051283 · Cited by 12 · see citing works
Design and characterization of 4D-710, an aerosolized gene therapy for cystic fibrosis lung disease
Calton, M. A., Croze, R. H., Sullivan, T. H., Collins, S., Tucker, S., Whittlesey, K. J., Kim, D. H., Nye, J. A., Beliakoff, G., Quezada, M., et al. (2025) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2025-0243ma · Cited by 9 · see citing works
Lopes‐Pacheco, M., Kitoko, J. Z., Morales, M. M., Petrs‐Silva, H., & Rocco, P. R. M. (2018) · Experimental Cell Research · doi:10.1016/j.yexcr.2018.09.015 · Cited by 10 · see citing works
A novel translational model for fetoscopic intratracheal delivery of nanoparticles in piglets
Carlon, M. S., Engels, A., Bosch, B., Joyeux, L., da Cunha, M. G. M. C. M., Vidović, D., Debyser, Z., Boeck, K. D., Neyrinck, A., & Deprest, J. A. (2016) · Prenatal Diagnosis · doi:10.1002/pd.4915 · Cited by 8 · see citing works
Self-citationRecent advances in host-focused molecular tools for investigating host-gut microbiome interactions
Wang, S., Gong, X., Xiao, F., & Yang, Y. K. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1335036 · Cited by 8 · see citing works
Ohira, S., Yokoi, Y., Ayabe, T., & Nakamura, K. (2022) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2022.11.008 · Cited by 7 · see citing works
Analysis of nasal potential in murine cystic fibrosis models
da Cunha, M. F., Simonin, J., Sassi, A., Freund, R., Hatton, A., Cottart, C., Elganfoud, N., Zoubaïri, R., Dragu, C., Jaïs, J., et al. (2016) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2016.10.001 · Cited by 7 · see citing works
Self-citationGene Therapy with Adeno-associated Virus for Cystic Fibrosis
Karda, R., Buckley, S. M. K., & Waddington, S. N. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201510-2024ed · Cited by 7 · see citing works
Organoid-on-a-chip (OrgOC): Advancing cystic fibrosis research
Zheng, M., Erice, E., Wang, H., Zhang, L., & Lawrie, C. H. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.102148 · Cited by 8 · see citing works
(2019) · Cellular Physiology and Biochemistry · doi:10.33594/000000089 · Cited by 5 · see citing works
Organoid transduction using recombinant adeno‐associated viral vectors: Challenges and opportunities
Belova, L., Лавров, А. В., & Smirnikhina, S. (2022) · BioEssays · doi:10.1002/bies.202200055 · Cited by 5 · see citing works
Cystic fibrosis as a paradigmatic disease in bringing science to the bedside
Amaral, M. D., & Pankonien, I. (2025) · FEBS Letters · doi:10.1002/1873-3468.70101 · Cited by 4 · see citing works
Graves, L. E., Viswanath, L., van Dijk, E. B., Zhu, E., Koyyalamudi, S. R., Wotton, T., Rosser, S. P. A., Srinivasan, S., Ginn, S. L., & Alexander, I. E. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.11.011 · Cited by 4 · see citing works
Diep, T., Zhou, W., Reyes, R. E., Nitzahn, M., Day, I. L., Makris, G., Lueptow, L. M., Zhuravka, I., Bakshi, S., Gangoiti, J. A., et al. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102470 · Cited by 4 · see citing works
Advancing cystic fibrosis treatment: investigational agents on the horizon
Santos, L., Camargo, M., Terlizzi, V., & Lopes‐Pacheco, M. (2025) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2025.2538275 · Cited by 3 · see citing works
Uta Griesenbach, D., McLachlan, G., Sinadinos, A., Cheminay, C., Ashour, J., Cox, J., Schwotzer, D., Vyhnal, K. K., Gupta, A., Chan, M., et al. (2025) · Molecular Therapy Advances · doi:10.1016/j.omta.2025.201655 · Cited by 2 · see citing works
Belova, L., Demchenko, A. G., Erofeeva, A., Kochergin-Nikitsky, K. S., Zubkova, O. V., Popova, O. D., Ozharovskaia, T. A., Salikhova, D. I., Efremova, A. S., Лавров, А. В., et al. (2025) · Biomedicines · doi:10.3390/biomedicines13040879 · Cited by 2 · see citing works
Nasal Potential Difference to Quantify Trans-epithelial Ion Transport in Mice
Beka, M., & Leal, T. (2018) · Journal of Visualized Experiments · doi:10.3791/57934 · Cited by 2 · see citing works
Systemic bis-phosphinic acid derivative restores chloride transport in Cystic Fibrosis mice
da Cunha, M. F., Pranke, I. M., Sassi, A., Schreiweis, C., Moriceau, S., Vidović, D., Hatton, A., Carlon, M. S., Creste, G., Berhal, F., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-09678-9 · Cited by 2 · see citing works
Self-citationMulti-Organ Pathogenesis and Therapeutic Strategies for Cystic Fibrosis
Babatunde, O., David, O. W., Ikwugbado, R. I., & Oyewole, O. (2024) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2024.125024 · Cited by 1 · see citing works
Nouvelles techniques d'évaluation dans la mucoviscidose
Dournes, G., Boeck, K. D., Bui, S., Vermeulen, F. L., Ramalho, A. S., Chateil, J., Laurent, F., & Fayon, M. J. (2016) · Archives de Pédiatrie · doi:10.1016/s0929-693x(17)30061-1 · Cited by 1 · see citing works
Self-citationDahariya, S., & Nagarjuna, V. (2021) · Springer eBooks · doi:10.1007/978-981-16-0002-9_14 · Cited by 1 · see citing works
Perspectives on Genetic Medicine for Cystic Fibrosis
Smirnikhina, S. (2022) · Current Gene Therapy · doi:10.2174/1566523222666220720102556 · Cited by 1 · see citing works
Nanoblades allow high-level genome editing in organoidsPreprint
Tirolle, V., Krug, A., Bokobza, E., Bulcaen, M., Ensinck, M. M., Geurts, M. H., Hendriks, D. F. G., Vermeulen, F. L., Larbret, F., Gutiérrez-Guerrero, A., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.04.502859 · Cited by 1 · see citing works
Self-citationCFTR functional assays in drug development
Zak, S. M., Clancy, J. P., & Brewington, J. J. (2017) · Expert Opinion on Orphan Drugs · doi:10.1080/21678707.2017.1393413
Prospects for using gene therapy drugs in the treatment of cystic fibrosis
Demidova, A. D., & Zavadskiy, S. P. (2025) · Farmacevticheskoe delo i tehnologija lekarstv (Pharmacy and Pharmaceutical Technology) · doi:10.33920/med-13-2501-04
Microphysiological systems to accelerate and de-risk AAV gene therapy development
Tornabene, P., Berreur, E., Roth, A., & Kasendra, M. J. (2026) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2026.115841
Umbach, A., Santini, A., Bulcaen, M., Guidone, D., Maule, G., Arosio, D., Carrozzo, I., Ciciani, M., Brugnara, E., Ramalho, A. S., et al. (2026) · Science Translational Medicine · doi:10.1126/scitranslmed.adw8886
Self-citationNucleic acid-based therapeutic strategies for modulator-refractory cystic fibrosis-causing variants
Leahy, M. D., Zollo, I., Clarke, L. A., & Farinha, C. M. (2026) · Human Molecular Genetics · doi:10.1093/hmg/ddag058 · Cited by 1 · see citing works
- Authors
- Vidović, D., Carlon, M. S., da Cunha, M. F., Dekkers, J. F., Hollenhorst, M. I., Bijvelds, M. J. C., Ramalho, A. S., Van den Haute, C., Ferrante, M., Baekelandt, V., Janssens, H. M., De Boeck, K., Sermet-Gaudelus, I., de Jonge, H. R., Gijsbers, R., Beekman, J. M., Edelman, A., & Debyser, Z.
- Affiliations
- Molecular Virology and Gene Therapy
- INSERM U1151, University Paris Descartes, Faculté de Médecine Necker Enfants-Malades, Paris, France
- University Medical Center Utrecht (NL)
- Inserm (FR)
- Erasmus MC (NL)
- Stem Cell Biology and Embryology
- Neurobiology and Gene Therapy
- KU Leuven (BE)
- University Hospital Leuven, Flanders, Belgium
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
- Corresponding author
- Debyser, Zeger
- ORCID
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-02-01
- Volume
- 193
- Issue
- 3
- Pages
- 288-298
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W1851407914
- Cited by
- 74
- References
- 68
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 5 · 2020: 4 · 2019: 8 · 2018: 3 · 2017: 8 · 2016: 10
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- green
- dspace.library.uu.nl
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Lirias (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- KU Leuven (DBOF/10/062)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- cystic fibrosis, recombinant adeno-associated virus, CFTR gene therapy, intestinal organoids, chloride secretion, fluid secretion, nasal potential difference, nasal mucosa
- MeSH terms
- Dependovirus, Animals, Body Fluids, Chlorides, Cystic Fibrosis, Disease Models, Animal, Colforsin, Genetic Vectors, Genotype, HeLa Cells, Humans, Intestines, Organoids, Transduction, Genetic, Genetic Therapy, Gene Transfer Techniques, Chloride Channels, Mice
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
