Chemically modified hCFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis
Open accessAbstract
Abstract Gene therapy has always been a promising therapeutic approach for Cystic Fibrosis (CF). However, numerous trials using DNA or viral vectors encoding the correct protein resulted in a general low efficacy. In the last years, chemically modified messenger RNA (cmRNA) has been proven to be a highly potent, pulmonary drug. Consequently, we first explored the expression, function and immunogenicity of human (h)CFTR encoded by cmRNAhCFTRin vitro and ex vivo, quantified the expression by flow cytometry, determined its function using a YFP based assay and checked the immune response in human whole blood. Similarly, we examined the function of cmRNAhCFTRin vivo after intratracheal (i.t.) or intravenous (i.v.) injection of the assembled cmRNAhCFTR together with Chitosan-coated PLGA (poly-D, L-lactide-co-glycolide 75:25 (Resomer RG 752 H)) nanoparticles (NPs) by FlexiVent. The amount of expression of human hCFTR encoded by cmRNAhCFTR was quantified by hCFTR ELISA, and cmRNAhCFTR values were assessed by RT-qPCR. Thereby, we observed a significant improvement of lung function, especially in regards to FEV0.1, suggesting NP-cmRNAhCFTR as promising therapeutic option for CF patients independent of their CFTR genotype.
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?
Restored lung function in CF was determined by increasing CFTR expression and improved forced expiratory volume.
“The restored lung function was determined by increasing CFTR expression and improved forced expiratory volume (FEV).[149]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [149]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 54 · Cited by 80
Research works printed but not linked: 1
- [17]Alton, E. et al. In A randomised, double-blind, placebo-controlled trial of repeated nebulisation of non-viral cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy in patients with cystic fibrosis (NIHR Journals Library Copyright (c) Queen’s Printer and Controller of HMSO 2016. This work was produced by Alton et al. under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK., 2016). 27441329
- Authors
- Haque, A. K. M. A., Dewerth, A., Antony, J. S., Riethmüller, J., Schweizer, G. R., Weinmann, P., Latifi, N., Yasar, H., Pedemonte, N., Sondo, E., Weidensee, B., Ralhan, A., Laval, J., Schlegel, P., Seitz, C., Loretz, B., Lehr, C.-M., Handgretinger, R., & Kormann, M. S. D.
- Affiliations
- University of Tübingen (DE)
- Helmholtz Centre for Infection Research (DE)
- Istituto Giannina Gaslini (IT)
- Corresponding author
- Kormann, Michael S. D.
- ORCID
- Venue
- Scientific Reports
- Published
- 2018-11-13
- Volume
- 8
- Issue
- 1
- Pages
- 16776-16776
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6233194
- OpenAlex
- W2899549605
- Cited by
- 80
- References
- 54
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 11 · 2023: 10 · 2022: 21 · 2021: 8 · 2020: 12 · 2019: 9 · 2018: 1
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- HZI (Helmholtz Centre for Infection Research) (submittedVersion, cc-by-nc-sa)
- Funders
- Deutsche Forschungsgemeinschaft (4258/2-1)
- EC | European Research Council (637752)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- cystic fibrosis, CFTR, chemically modified mRNA, intratracheal administration, lung function, CFTR expression, CFTR function, immunogenicity, mouse model
- MeSH terms
- Animals, Cell Line, Cystic Fibrosis, Disease Models, Animal, Humans, Lung, Maximal Expiratory Flow Rate, RNA, Messenger, Genetic Therapy, Cystic Fibrosis Transmembrane Conductance Regulator, 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
