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:10.1101/2024.01.22.576687

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High ionic strength vector formulations enhance gene transfer to airway epithelia

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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

bioRxiv : the preprint server for biology

Cold Spring Harbor Laboratory

01/23/2024

DOI: 10.1101/2024.01.22.576687

PMCID: PMC10849541

PMID: 38328187

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https://doi.org/10.1101/2024.01.22.576687View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

A fundamental challenge for cystic fibrosis (CF) gene therapy is ensuring sufficient ransduction 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 unctions, 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 hree 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 nvolved 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.One Sentence SummaryFormulating adenoviral, AAV, and lentiviral vectors with hypertonic saline remarkably enhances lung gene transfer. (114 characters, including spaces).

Details

Title: Subtitle: High ionic strength vector formulations enhance gene transfer to airway epithelia
Creators: Ashley L Cooney - University of Iowa
Laura Marquez Loza
Kenan Najdawi - University of Iowa
Christian M Brommel - University of Iowa
Paul B McCray - University of Iowa
Patrick L Sinn - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv : the preprint server for biology
DOI: 10.1101/2024.01.22.576687
PMID: 38328187
PMCID: PMC10849541
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 01/23/2024
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Orthopedics and Rehabilitation; Internal Medicine
Record Identifier: 9984557960202771

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