Abstract
502. Formulation of adenoviral vectors with inhibitors of mucociliary clearance enhances gene transfer to airway epithelia in vivo
Molecular therapy, Vol.9(S1), pp.S190-S191
05/01/2004
DOI: 10.1016/j.ymthe.2004.06.439
Abstract
Mucociliary clearance and other pulmonary innate defense mechanisms pose significant barriers to gene transfer vectors. We previously demonstrated that Ca2+ chelators such as EGTA enhance gene transfer to well differentiated airway epithelia. This effect may result from the combined effects of cilia stasis and the opening of epithelial tight junctions. Furthermore, adenoviral vectors formulated with Avicel type RC-591 containing gel have been previously demonstrated to enhance gene transfer to airway epithelia. We tested the gene transfer enhancing properties of several viscoelastic gels by formulating them with an adenoviral vector expressing nuclear targeted b-galactosidase. The reagents included methylcellulose, carboxymethylcellulose, and Pluronic® F127. These formulations were compared to 400 mM EGTA, Avicel type RC-591, and no formulation controls. We delivered the vector solutions to mice via tracheal intubation and 4 days later measured b-galactosidase expression by enzyme activity assay or X-gal staining. With each of the gels tested, gene transfer equaled or exceeded that observed with the positive controls. Gene expression from gel formulated vectors was largely confined to the conducting airways. As added confirmation of the results, the gels were formulated with an adenoviral vector expressing firefly luciferase and in vivo gene transfer was detected using bioluminescent imaging 4 days later with a CCD camera. Currently, we are testing the utility of similar gel formulations in enhancing the gene transfer with other classes of gene transfer vectors. In conclusion, vector formulations designed to inhibit mucociliary clearance enhance gene transfer to the conducting airways in vivo.
Details
- Title: Subtitle
- 502. Formulation of adenoviral vectors with inhibitors of mucociliary clearance enhances gene transfer to airway epithelia in vivo
- Creators
- Patrick L SinnAnkur ShahMaureen D DonovanPaul B McCray Jr
- Resource Type
- Abstract
- Publication Details
- Molecular therapy, Vol.9(S1), pp.S190-S191
- Publisher
- Elsevier Limited
- DOI
- 10.1016/j.ymthe.2004.06.439
- ISSN
- 1525-0016
- eISSN
- 1525-0024
- Language
- English
- Date published
- 05/01/2004
- Academic Unit
- Microbiology and Immunology; Internal Medicine; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Pulmonary Medicine
- Record Identifier
- 9984297543502771
Metrics
9 Record Views