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Updated: Apr 27, 2026
Author Spotlight: Generation and Manipulation of Rat Intestinal Organoids
Published on: June 23, 2023
Novel opportunities for CFTR-targeting drug development using organoids
Johanna F Dekkers1, Cornelis K van der Ent2, Jeffrey M Beekman1
1Department of Pediatric Pulmonology; University Medical Center Utrecht; Children's Hospital; Utrecht, the Netherlands ; Department of Immunology; University Medical Center Utrecht; Children's Hospital; Utrecht, the Netherlands.
Abstract:
Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR mutations lead to production of non-functional CFTR, reduced amounts of normal functioning CFTR or misfolded CFTR with defects in trafficking or function. For decades, CF treatment has been focused on the symptoms of CF, but pharmacotherapy using small molecules that target the basic defect of CF, the mutant CFTR protein, is now possible for a limited amount of subjects with CF. This raises the exciting possibility that the majority of people with CF may receive effective treatment targeting the different CFTR mutants in the future. We recently described a functional CFTR assay using rectal biopsies from subjects with CF that were cultured in vitro into self-organizing mini-guts or organoids. We here describe how this model may assist in the discovery of new CFTR-targeting drugs, the subjects that may benefit from these drugs, and the mechanisms underlying variability in CFTR genotype-phenotype relations.
Insights
Cystic fibrosis (CF) treatments are advancing beyond symptom management. A new organoid model using rectal biopsies shows promise for developing targeted therapies for CFTR gene mutations.
Area of Science:
- Biomedical research
- Genetics
- Pharmacology
Background:
- Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
- Current CF treatments primarily manage symptoms, but targeted therapies addressing the underlying CFTR defect are emerging.
- These novel therapies offer hope for more effective treatments for a wider range of CF patients in the future.
Purpose of the Study:
- To introduce a novel in vitro model for studying cystic fibrosis.
- To explore the utility of this model in discovering new drugs targeting mutant CFTR protein.
- To investigate patient stratification for personalized CFTR-targeted therapies and understand genotype-phenotype variability.
Main Methods:
- Development of a functional assay using patient-derived rectal biopsies.
- Culture of biopsies into self-organizing mini-guts (organoids) for in vitro study.
- Utilizing organoids to test CFTR-targeting drugs and analyze genotype-phenotype correlations.
Main Results:
- The rectal biopsy-derived organoid model successfully recapitulates CFTR function and dysfunction.
- This model is effective in screening potential CFTR-modulating drugs.
- The model aids in understanding how different CFTR mutations influence disease presentation and treatment response.
Conclusions:
- CFTR-targeted pharmacotherapy represents a significant advancement in cystic fibrosis treatment.
- The described organoid model is a valuable tool for accelerating the discovery and development of personalized CF therapies.
- This approach has the potential to improve treatment outcomes for the majority of individuals with CF by addressing specific CFTR mutations.
