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- Title
Nacystelyn enhances adenoviral vector-mediated gene delivery to mouse airways.
- Authors
Kushwah, R.; Oliver, J. R.; Cao, H.; Hu, J.
- Abstract
Adenoviral vector-mediated gene delivery has been vastly investigated for cystic fibrosis (CF) gene therapy; however, one of its drawbacks is the low efficiency of gene transfer, which is due to basolateral colocalization of viral receptors, immune responses to viral vectors and the presence of a thick mucus layer in the airways of CF patients. Therefore, enhancement of gene transfer can lead to reduction in the viral dosage, which could further reduce the acute toxicity associated with the use of adenoviral vectors. Nacystelyn (NAL) is a mucolytic agent with anti-inflammatory and antioxidant properties, and has been used clinically in CF patients to reduce mucus viscosity in the airways. In this study, we show that pretreatment of the airways with NAL followed by administration of adenoviral vectors in complex with DEAE-Dextran can significantly enhance gene delivery to the airways of mice without any harmful effects. Moreover, NAL pretreatment can reduce the airway inflammation, which is normally observed after delivery of adenoviral particles. Taken together, these results indicate that NAL pretreatment followed by adenoviral vector-mediated gene delivery can be beneficial to CF patients by increasing the efficiency of gene transfer to the airways, and reducing the acute toxicity associated with the administration of adenoviral vectors.Gene Therapy (2007) 14, 1243–1248; doi:10.1038/sj.gt.3302968; published online 24 May 2007
- Subjects
ADENOVIRUSES; CYSTIC fibrosis; GENE therapy; AIRWAY (Anatomy); GENETIC transformation; IMMUNE response; LABORATORY mice
- Publication
Gene Therapy, 2007, Vol 14, Issue 16, p1243
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3302968