Translational research to enable personalized treatment of cystic fibrosis
Open accessAbstract
Translational research efforts in cystic fibrosis (CF) aim to develop therapies for all subjects with CF. To reach this goal new therapies need to be developed that target multiple aspects of the disease. To enable individuals to benefit maximally from these treatments will require improved methods to tailor these therapies specifically to individuals who suffer from CF. This report highlights current examples of translational CF research efforts to reach this goal. The use of intestinal organoids and genetics to better understand individual assessment of CFTR modulator treatment effects to ultimately enable a better personalized treatment for CF subjects will be discussed. In addition, development of viral vectors and non-viral synthetic nanoparticles for delivery of mRNA, sgRNA and DNA will be highlighted. New approaches to restore function of CFTR with early premature termination codons using nanoparticle delivery of suppressor tRNAs and new insights into mechanisms of airway epithelial repair will be reviewed as well. The state-of-the-art approaches that are discussed in this review demonstrate significant progress towards the development of optimal individual therapies for CF patients, but also reveal that remaining challenges still lie ahead.
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Small molecules that restore chloride transport function of mutant CFTR have shown promising clinical results, but their narrow application range, poor improvements in lung function, and side effects limit their utilization.
“Some small molecules that aim to restore the chloride transport function of the mutant CFTR have shown promising clinical results. However, their narrow application range, poor improvements in lung function, and side effects limit their utilization.[188–190]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [190]
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Lipid Nanoparticle-Delivered Chemically Modified mRNA Restores Chloride Secretion in Cystic Fibrosis
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- Authors
- Hagemeijer, M. C., Siegwart, D. J., Strug, L. J., Cebotaru, L., Torres, M. J., Sofoluwe, A., & Beekman, J. M.
- Affiliations
- University Medical Center Utrecht (NL)
- Harold C. Simmons Comprehensive Cancer Center (US)
- University of Toronto (CA)
- Johns Hopkins University (US)
- University of Geneva (CH)
- Corresponding author
- Beekman, Jeffrey M.
- Venue
- Journal of Cystic Fibrosis
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 17
- Issue
- 2
- Pages
- S46-S51
- ISSN
- 1569-1993 (ISSN-L)
- OpenAlex
- W2781035400
- Cited by
- 22
- References
- 31
- Citations by year
- 2025: 2 · 2024: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 8 · 2017: 1
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Cystic Fibrosis (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- Canadian Institutes of Health Research (MOP-258916)
- Natural Sciences and Engineering Research Council of Canada (371399-2009)
- Cystic Fibrosis Canada (2626)
- Cancer Prevention and Research Institute of Texas (R1212)
- Horizon 2020 Framework Programme (633545)
- Cystic Fibrosis Foundation
- Wilhelmina Kinderziekenhuis
- Welch Foundation (I-1855)
- Mary Kay Foundation (049-15)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030_153342)
- National Institutes of Health (R01 HL 122267)
- ZonMw (40-00812-98-14103)
- American Cancer Society (RSG-17-012-01)
- Stavros Niarchos Foundation
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- personalized medicine, CFTR modulators, intestinal organoids, CFTR function, viral vectors, mRNA delivery, DNA delivery, suppressor tRNA, premature stop codon, airway epithelial repair, translational research
- MeSH terms
- Cystic Fibrosis, Humans, Mutation, Genetic Therapy, Cystic Fibrosis Transmembrane Conductance Regulator, Translational Research, Biomedical, Precision Medicine
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