High ionic strength vector formulations enhance gene transfer to airway epithelia

Ashley L Cooney; Laura Marquez Loza; Kenan Najdawi; Christian M Brommel; Paul B McCray; Patrick L Sinn

doi:10.1093/nar/gkae640

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High ionic strength vector formulations enhance gene transfer to airway epithelia

Journal article

Open access

Peer reviewed

High ionic strength vector formulations enhance gene transfer to airway epithelia

Ashley L Cooney, Laura Marquez Loza, Kenan Najdawi, Christian M Brommel, Paul B McCray and Patrick L Sinn

Nucleic acids research, Vol.52(16), pp.9369-9383

09/09/2024

DOI: 10.1093/nar/gkae640

PMCID: PMC11381324

PMID: 39077931

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Abstract

Abstract A fundamental challenge for cystic fibrosis (CF) gene therapy is ensuring sufficient transduction of airway epithelia to achieve therapeutic correction. Hypertonic saline (HTS) is frequently administered to people with CF to enhance mucus clearance. HTS transiently disrupts epithelial cell tight junctions, but its ability to improve gene transfer has not been investigated. Here, we asked if increasing the concentration of NaCl enhances the transduction efficiency of three gene therapy vectors: adenovirus, AAV, and lentiviral vectors. Vectors formulated with 3–7% NaCl exhibited markedly increased transduction for all three platforms, leading to anion channel correction in primary cultures of human CF epithelial cells and enhanced gene transfer in mouse and pig airways in vivo. The mechanism of transduction enhancement involved tonicity but not osmolarity or pH. Formulating vectors with a high ionic strength solution is a simple strategy to greatly enhance efficacy and immediately improve preclinical or clinical applications.

Details

Title: Subtitle: High ionic strength vector formulations enhance gene transfer to airway epithelia
Creators: Ashley L Cooney - University of Iowa, Stead Family Department of Pediatrics
Laura Marquez Loza
Kenan Najdawi - University of Iowa
Christian M Brommel
Paul B McCray - University of Iowa
Patrick L Sinn - University of Iowa, Pulmonary Medicine
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.52(16), pp.9369-9383
DOI: 10.1093/nar/gkae640
PMID: 39077931
PMCID: PMC11381324
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Language: English
Electronic publication date: 07/30/2024
Date published: 09/09/2024
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Orthopedics and Rehabilitation; Internal Medicine
Record Identifier: 9984691439102771

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