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Comparison of physical perturbation devices for enhancing lentiviral vector-mediated gene transfer to the airway epithelium.

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dc.contributor.authorDrysdale, V.
dc.contributor.authorCmielewski, P.
dc.contributor.authorDonnelley, M.
dc.contributor.authorReyne, N.
dc.contributor.authorParsons, D.
dc.contributor.authorMcCarron, A.
dc.date.issued2022
dc.description.abstractNatural airway defenses currently impede the efficacy of viral vector-mediated airway gene therapy. Conditioning airways before vector delivery can disrupt these barriers, improving viral vector access to target receptors and airway stem cells. This study aimed to assess and quantify the in vivo histological and gene transfer effects of physical perturbation devices to identify effective conditioning approaches. A range of flexible wire baskets with varying configurations, a Brush, biopsy forceps, and a balloon catheter were examined. We first evaluated the histological effects of physical perturbation devices in rat tracheas that were excised 10 min after conditioning. Based on the histological findings, a selection of devices was used to condition rat tracheas in vivo before delivering a lentiviral vector containing the LacZ reporter gene. After 7 days, excised tracheas were X-gal processed and examined en face to quantify the area of LacZ staining. Histological observations 10 min after conditioning found that physical perturbation dislodged cells from the basement membrane to varying degrees, with some producing significant levels of epithelial cell removal. When a subset of devices was assessed for their ability to enhance gene transfer, only the NGage® wire basket (Cook Medical) produced a significant increase in the proportion of X-gal-stained area when compared with unconditioned tracheas (eightfold, p = 0.00025). These results suggest that a range of factors contribute to perturbation-enhanced gene transfer. Overall, this study supports existing evidence that physical perturbation can assist airway gene transfer and will help to identify the characteristics of an effective device for airway gene therapy.
dc.description.statementofresponsibilityVictoria Drysdale, Patricia Cmielewski, Martin Donnelley, Nicole Reyne, David Parsons, and Alexandra McCarron
dc.identifier.citationHuman Gene Therapy, 2022; 33(19-20):1062-1072
dc.identifier.doi10.1089/hum.2022.086
dc.identifier.issn1043-0342
dc.identifier.issn1557-7422
dc.identifier.orcidCmielewski, P. [0000-0002-2236-9410]
dc.identifier.orcidDonnelley, M. [0000-0002-5320-7756]
dc.identifier.orcidReyne, N. [0000-0002-3487-0827]
dc.identifier.orcidParsons, D. [0000-0002-8775-3501] [0000-0003-1746-3290]
dc.identifier.orcidMcCarron, A. [0000-0002-6045-3998]
dc.identifier.urihttps://hdl.handle.net/2440/145861
dc.language.isoen
dc.publisherMary Ann Liebert
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT1160011
dc.rights© 2022 by Mary Ann Liebert, Inc.
dc.source.urihttps://doi.org/10.1089/hum.2022.086
dc.subjectlentiviral vector; gene therapy; airway; epithelium; perturbation; rat
dc.subject.meshTrachea
dc.subject.meshEpithelium
dc.subject.meshAnimals
dc.subject.meshRats
dc.subject.meshLentivirus
dc.subject.meshGene Transfer Techniques
dc.subject.meshTransduction, Genetic
dc.subject.meshGenetic Vectors
dc.subject.meshGenetic Therapy
dc.titleComparison of physical perturbation devices for enhancing lentiviral vector-mediated gene transfer to the airway epithelium.
dc.typeJournal article
pubs.publication-statusPublished

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