title: Modification of liposomal concentration in liposome/adenoviral complexes allows significant protection of adenoviral vectors from neutralising antibody, in vitro.
abstract: Adenoviral vectors have been commonly used in gene therapy protocols, however the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced which limits further administration. This study examines the efficacy of complexing liposomes to adenovirus for the protection of the adenovirus from neutralising antibodies in an in vitro setting. Dimethyldioctadecylammonium bromide (DDAB)-dioleoyl-l-phosphatidylethanolamine (DOPE) liposomes were bound at varying concentrations to adenovirus to form AL complexes and tested these complexes' ability to prevent adenoviral neutralisation. It is shown that by increasing the concentration of liposomes in the adenoviral-liposome (AL) complexes we can increase the level of immuno-shielding afforded the adenovirus. It is also shown that the increase in liposomal concentration may lead to drawbacks such as increased cytotoxicity and reductions in expression levels.
authors.affiliation: School of Biomedical Science, Charles Sturt University, P.O. Box 588, Wagga Wagga 2678, Australia. steeljas@mail.nih.gov
authors.forename: Jason C
authors.initials: JC
authors.lastname: Steel
authors.forename: Heather M A
authors.initials: HM
authors.lastname: Cavanagh
authors.forename: Mark A
authors.initials: MA
authors.lastname: Burton
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Dingwall
authors.forename: Wouter H J
authors.initials: WH
authors.lastname: Kalle
mesh_terms: D000256:Adenoviridae / Q000737:chemistry* / Q000276:immunology*; D002460:Cell Line; D015870:Gene Expression; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000276:immunology* / Q000633:toxicity; D009500:Neutralization Tests; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000276:immunology; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000276:immunology; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C094877:dioleoyl phosphatidylethanolamine; C015831:dimethyldioctadecylammonium; D001616:beta-Galactosidase