title: Improvement of adenoviral vector-mediated gene transfer to airway epithelia by folate-modified anionic liposomes.
abstract: Despite remarkable progress in the development of both viral and nonviral gene delivery vectors for airway disease treatment, poor gene transfer efficiency to the airway epithelium is a major obstacle in clinical application. To take advantage of the unique features of viral and nonviral vectors, we have developed complexes of adenovirus vector and anionic liposomes (AL-Ad5) by the calcium-induced phase change method. In the current study, based on the fact that there are overexpressed folate receptors on the surface of airway epithelia, we further modified the AL-Ad5 complexes with folate (F-AL-Ad5) to improve the transduction ability of Ad5 in airway epithelia. The transduction efficiencies of the obtained F-AL-Ad5 and AL-Ad5 complexes were assessed in primary-cultured airway epithelia in vitro. Our results indicated that compared with naked adenovirus vector, both AL-Ad5 and F-AL-Ad5 could significantly enhance the gene transduction efficiency of adenovirus vector in primary-cultured airway epithelial cells. Moreover, the enhancement mediated by F-AL-Ad5 was more dramatic than that by AL-Ad5. These results suggested that F-AL-Ad5 may be a useful strategy to deliver therapeutic genes to the airway epithelia and is promising in clinical application.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhong
authors.forename: Yu
authors.initials: Y
authors.lastname: Wan
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Han
authors.forename: Sanjun
authors.initials: S
authors.lastname: Shi
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D000838:Anions; D004492:Edetic Acid; D005434:Flow Cytometry; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D007763:Lac Operon; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D020545:Respiratory Mucosa / Q000166:cytology / Q000821:virology*
chemical_list: D000838:Anions; D008081:Liposomes; D005492:Folic Acid; D004492:Edetic Acid