title: Coagulation factor X shields adenovirus type 5 from attack by natural antibodies and complement.
abstract: Adenovirus type 5 (Ad5) specifically binds coagulation factor X (FX), and FX is normally essential for intravenously injected Ad5 vectors to transduce the liver. We demonstrate that the ability of FX to enhance liver transduction by Ad5 vectors is due to an unexpected ability of FX to protect Ad5 from attack by the classical complement pathway. In vitro, naive mouse serum neutralized Ad5 when FX was blocked from binding Ad5. This neutralization was mediated by natural IgM and the classical complement pathway. In vivo, FX was essential for Ad5 vectors to transduce the livers of wild-type mice, but FX was not required for liver transduction in mice that lack antibodies, C1q or C4. We conclude that Ad5 recruits FX as a defense against complement and that the sensitivity of Ad5 to inactivation by complement must be taken into account when designing vectors for systemic gene therapy.
authors.affiliation: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Xu
authors.forename: Qi
authors.initials: Q
authors.lastname: Qiu
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Smith
authors.forename: Gina M
authors.initials: GM
authors.lastname: Conenello
authors.forename: Takashi
authors.initials: T
authors.lastname: Morita
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Byrnes
mesh_terms: D000256:Adenoviridae / Q000276:immunology* / Q000378:metabolism; D000257:Adenoviridae Infections / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D005170:Factor X / Q000378:metabolism*; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID
chemical_list: D000914:Antibodies, Viral; D007075:Immunoglobulin M; D005170:Factor X; D003165:Complement System Proteins