High ionic strength vector formulations enhance gene transfer to airway epithelia.

Autor:	Cooney AL; University of Iowa, Stead Family Department of Pediatrics; Iowa City, IA 52242, USA.; University of Iowa, Pappajohn Biomedical Institute; Iowa City, IA 52242, USA., Loza LM; University of Iowa, Stead Family Department of Pediatrics; Iowa City, IA 52242, USA.; University of Iowa, Pappajohn Biomedical Institute; Iowa City, IA 52242, USA., Najdawi K; University of Iowa, Stead Family Department of Pediatrics; Iowa City, IA 52242, USA.; University of Iowa, Pappajohn Biomedical Institute; Iowa City, IA 52242, USA., Brommel CM; University of Iowa, Stead Family Department of Pediatrics; Iowa City, IA 52242, USA.; University of Iowa, Pappajohn Biomedical Institute; Iowa City, IA 52242, USA., McCray PB Jr; University of Iowa, Stead Family Department of Pediatrics; Iowa City, IA 52242, USA.; University of Iowa, Pappajohn Biomedical Institute; Iowa City, IA 52242, USA.; University of Iowa, Center for Gene Therapy; Iowa City, IA 52242, USA., Sinn PL; University of Iowa, Stead Family Department of Pediatrics; Iowa City, IA 52242, USA.; University of Iowa, Pappajohn Biomedical Institute; Iowa City, IA 52242, USA.; University of Iowa, Center for Gene Therapy; Iowa City, IA 52242, USA.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Sep 09; Vol. 52 (16), pp. 9369-9383.
DOI:	10.1093/nar/gkae640
Abstrakt:	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. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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