title: Immune Protection of Retroviral Vectors Upon Molecular Painting with the Complement Regulatory Protein CD59.
abstract: Glycosylphosphatidylinositol anchoring is a type of post-translational modification that allows proteins to be presented on the exterior side of the cell membrane. Purified glycosylphosphatidylinositol-anchored protein can spontaneously re-insert into lipid bilayer membranes in a process termed Molecular Painting. Here, we demonstrate the possibility of inserting purified, recombinant CD59 into virus particles produced from a murine retroviral producer cell line. CD59 is a regulator of the complement system that helps protect healthy cells from the lytic activity of the complement cascade. In this study, we could show that Molecular Painting confers protection from complement activity upon murine retroviral vector particles. Indeed, increased infectivity of CD59-modified virus particles was observed upon challenge with human serum, indicating that Molecular Painting is suitable for modulating the immune system in gene therapy or vaccination applications.
authors.affiliation: Institute of Virology, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Heider
authors.affiliation: Institute of Virology, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kleinberger
authors.affiliation: Institute of Virology, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria.
authors.forename: Feliks
authors.initials: F
authors.lastname: Kochan
authors.affiliation: Anovasia Pte. Ltd., 3 Biopolis Drive, #05-19 Synapse, Singapore, 138623, Singapore.
authors.forename: John A
authors.initials: JA
authors.lastname: Dangerfield
authors.affiliation: Institute of Virology, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria. christoph.metzner@vetmeduni.ac.at.
authors.forename: Christoph
authors.initials: C
authors.lastname: Metzner
mesh_terms: D000818:Animals; D018957:CD59 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003167:Complement Activation; D017261:Glycosylphosphatidylinositols / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014771:Virion / Q000276:immunology*
chemical_list: D018957:CD59 Antigens; D017261:Glycosylphosphatidylinositols; D008051:Lipid Bilayers; D011994:Recombinant Proteins; C051590:CD59 protein, human
keywords: CD59; Complement; Gene therapy; Molecular Painting; Protein engineering; Vaccination; Viral vectors