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Complexes of adenovirus with polycationic polymers and cationic lipids increase the efficiency of gene transfer in vitro and in vivo
Journal article   Open access   Peer reviewed

Complexes of adenovirus with polycationic polymers and cationic lipids increase the efficiency of gene transfer in vitro and in vivo

Al Fasbender, Joseph Zabner, Miguel Chillón, Thomas O Moninger, Aurita P Puga, Beverly L Davidson and Michael J Welsh
The Journal of biological chemistry, Vol.272(10), pp.6479-6489
03/07/1997
DOI: 10.1074/jbc.272.10.6479
PMID: 9045673
url
https://doi.org/10.1074/jbc.272.10.6479View
Published (Version of record) Open Access

Abstract

Improving the efficiency of gene transfer remains an important goal in developing new treatments for cystic fibrosis and other diseases. Adenovirus vectors and nonviral vectors each have specific advantages, but they also have limitations. Adenovirus vectors efficiently escape from the endosome and enter the nucleus, but the virus shows limited binding to airway epithelia. Nonviral cationic vectors bind efficiently to the negatively charged cell surface, but they do not catalyze subsequent steps in gene transfer. To take advantage of the unique features of the two different vector systems, we noncovalently complexed cationic molecules with recombinant adenovirus encoding a transgene. Complexes of cationic polymers and cationic lipids with adenovirus increased adenovirus uptake and transgene expression in cells that were inefficiently infected by adenovirus alone. Infection by both complexes was independent of adenovirus fiber and its receptor and occurred via a different cellular pathway than adenovirus alone. Complexes of cationic molecules and adenovirus also enhanced gene transfer to differentiated human airway epithelia in vitro and to the nasal epithelium of cystic fibrosis mice in vivo. These data show that complexes of adenovirus and cationic molecules increase the efficiency of gene transfer, which may enhance the development of gene therapy.
 Cystic Fibrosis Gene Transfer Techniques Cations - chemistry Culture Techniques Receptors, Virus - metabolism Humans Epithelium - ultrastructure Microscopy, Electron Animals Membrane Potentials Mice, Mutant Strains Capsid Proteins Polymers - chemistry Adenoviruses, Human - genetics Epithelium - physiology Mice HeLa Cells Capsid - metabolism Genetic Vectors COS Cells 3T3 Cells Genetic Therapy - methods

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