Journal article
LUNAR® LNP delivery of CFTR mRNA restores channel function and improves mucociliary clearance in human and ferret cystic fibrosis airways
Molecular therapy, Vol.34(4), pp.2044-2062
04/01/2026
DOI: 10.1016/j.ymthe.2025.12.040
PMCID: PMC12888765
PMID: 41445193
Abstract
Lipid nanoparticle (LNP)-based delivery of CFTR-mRNA holds promise for treating pulmonary manifestations of cystic fibrosis (CF). LUNAR®-CFTR is a novel proprietary lipid nanoparticle (LNP) encapsulating codon-optimized human CFTR mRNA for CFTR replacement therapy. In this study, we examined the potential of LUNAR®-CFTR for delivering mRNA and restoring CFTR function in primary human and ferret airway epithelial cells and mucus-laden CF ferret airways. LUNAR® effectively delivered CFTR, Cre, and tdTomato mRNAs into multiple airway epithelial cell types of human and ferret in vitro and transgenic ferrets in vivo. The LUNAR®-CFTR was able to restore ion transport in polarized CF human bronchial epithelia to levels comparable to those achieved with elexacaftor/tezacaftor/ivacaftor. Mucociliary clearance (MCC) assays in CF ferrets further showed that a single dose of LUNAR®-mediated human CFTR mRNA delivery improved mean MCC values by 3-fold. The improved MCC was in line with an increase in CFTR-mediated transepithelial anion transport from the CF ferret trachea transfected with LUNAR®-CFTR in vivo. These findings underscore the potential of LUNAR® LNP as a robust vehicle for delivering CFTR-encoding therapeutic mRNA into airway epithelial cells and underscore the utility of CF ferrets as a reliable tool to evaluate the efficiency of gene therapy in mucus-laden airways.
Details
- Title: Subtitle
- LUNAR® LNP delivery of CFTR mRNA restores channel function and improves mucociliary clearance in human and ferret cystic fibrosis airways
- Creators
- Xiaoming Liu - University of IowaJavier Campos-Gomez - University of Alabama at BirminghamMeihui Luo - University of IowaJia Ma - University of IowaHan-Chung Chen - University of Alabama at BirminghamSourabh Shukla - Arcturus Therapeutics (United States)Shuang Wu - University of IowaGuy Snow - University of IowaYihua Pei - Arcturus Therapeutics (United States)Stefen A Boehme - Arcturus Therapeutics (United States)David E Geller - Arcturus Therapeutics (United States)Steve M Rowe - Cystic Fibrosis FoundationJohn F Engelhardt - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular therapy, Vol.34(4), pp.2044-2062
- DOI
- 10.1016/j.ymthe.2025.12.040
- PMID
- 41445193
- PMCID
- PMC12888765
- NLM abbreviation
- Mol Ther
- ISSN
- 1525-0024
- eISSN
- 1525-0024
- Publisher
- Elsevier
- Grant note
- Arcturus Therapeutics National Institutes of Health: R35HL135816, P30 DK072482, P30 DK054759, HL152960, HL165404 NHLBI: 75N92025C00007 Cystic Fibrosis Foundation: CFF/ROWE17XX1, CFF/ROWE19R0, ENGELH21XX0
This work was primarily funded by sponsored research agreements with Arcturus Therapeutics (to X.L. and J.C.-G.) . Other funded agencies also contributed in part including the National Institutes of Health R35HL135816, P30 DK072482 (to S.M.R.) , P30 DK054759, HL152960, HL165404, and NHLBI contract 75N92025C00007 (to J.F.E.) , and the Cystic Fibrosis Foundation CFF/ROWE17XX1, CFF/ROWE19R0 (to S.M.R.) and ENGELH21XX0 (to J.F.E.) . This study was performed according to protocols approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Iowa and conforms to National Institutes of Health (NIH) standards (Protocol ID1071945) . Humane/euthanasia endpoints: labored breathing with a respiratory rate greater than 90 bpm or lack of movement or response upon stimulation.
- Language
- English
- Electronic publication date
- 12/24/2025
- Date published
- 04/01/2026
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9985093889702771
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