Journal article
CFTR gene delivery to human airway epithelia using parainfluenza virus 5 amplifying virus-like particles
Molecular therapy. Nucleic acids, Vol.37(3), 102975
09/08/2026
DOI: 10.1016/j.omtn.2026.102975
PMID: 42376650
Abstract
Parainfluenza virus 5 (PIV5)-derived amplifying virus-like particles (PIV5-AVLPs) are an efficient gene delivery platform with broad cell tropism. To investigate the feasibility of using PIV5-AVLPs for cystic fibrosis (CF) gene therapy, we generated AVLPs expressing enhanced green fluorescent protein (AVLP-eGFP) or a codon-optimized human cystic fibrosis transmembrane conductance regulator (CFTR) coding sequence and an mCherry reporter (AVLP-CFTR). We examined the transduction efficiency and persistence of transgene expression of AVLP-eGFP in primary cultures of non-CF and CF human airway epithelia (HAE). When applied to the apical surface of HAE, the AVLP-eGFP mainly transduced ciliated epithelial cells, with lesser targeting to secretory and basal cells. Reporter transgene expression gradually diminished over a 1-month time course. Transducing approximately 15% of CF airway epithelial cells with AVLP-CFTR was sufficient to restore CFTR-dependent short-circuit current to levels similar to non-CF epithelia. Our results demonstrate that PIV5-AVLPs delivered to the apical side of HAE efficiently transduce sufficient epithelial cells to restore functional CFTR expression. PIV5-based AVLPs provide a versatile platform for the delivery of a variety of genetic cargoes to the respiratory tract.
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McCray and colleagues demonstrate the ability of single-cycle parainfluenza virus 5 (PIV5) vectors to deliver large nucleic acid cargoes to target cells. They generated vectors encoding a full-length CFTR cDNA and showed that they could correct CFTR-dependent anion transport without causing cytopathic effects in primary human airway epithelial cells.
Details
- Title: Subtitle
- CFTR gene delivery to human airway epithelia using parainfluenza virus 5 amplifying virus-like particles
- Creators
- Mark A. Phillips - University of GeorgiaLei Lei - University of IowaKatarina Kulhankova - University of IowaMaría Cristina Gingerich - University of GeorgiaLaura Marquez Loza - Stead Family Department of Pediatrics and Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa, IA 52242, USAAmber Vu - University of IowaBiao He - University of GeorgiaIan M. Thornell - University of IowaPaul B. McCray - Stead Family Department of Pediatrics and Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Molecular therapy. Nucleic acids, Vol.37(3), 102975
- DOI
- 10.1016/j.omtn.2026.102975
- PMID
- 42376650
- NLM abbreviation
- Mol Ther Nucleic Acids
- ISSN
- 2162-2531
- eISSN
- 2162-2531
- Publisher
- Elsevier Inc
- Grant note
- National Institutes of Health: P01 HL152960, P01 HL091842, P30 DK054759, R01 HL173260, F31 HL152500, THORNE24G0, STOLTZ23R0 Roy J. Carver Chair in Pulmonary Research: F31 HL152500 Fred C. Davison Distinguished University Chair in Veterinary Medicine: THORNE24G0, STOLTZ23R0
We thank Jennifer Bartlett and Patrick Sinn for critical review of the manuscript. This work was supported by the National Institutes of Health (to P.B.M. Jr.: P01 HL152960, P01 HL091842, and P30 DK054759; to I.M.T.: R01 HL173260, Cystic Fibrosis Foundation [THORNE24G0], Cystic Fibrosis Foundation University of Iowa RDP (STOLTZ23R0); and to L.M.L.: F31 HL152500). P.B.M. Jr. is supported by the Roy J. Carver Chair in Pulmonary Research. B.H. is supported by Fred C. Davison Distinguished University Chair in Veterinary Medicine.
- Language
- English
- Date published
- 09/08/2026
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9985176653502771
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