Targeting of adenovirus serotype 5 (Ad5) and 5/47 pseudotyped vectors in vivo: fundamental involvement of coagulation factors and redundancy of CAR binding by Ad5.
Vitamin K-dependent coagulation factors can promote adenoviral cell transduction in vitro. In vivo, warfarin pretreatment ablates liver targeting of an adenovirus serotype 5 (Ad5) vector deleted of CAR binding capability. Here, we assess in vivo transduction and biodistribution of Ad5 vectors with nonmodified fibers (Ad5) and a serotype 47 fiber-pseudotyped Ad5 (Ad5/47; subgroup D) virus following intravascular injection. Warfarin reduced liver transduction by both viruses. However, no impact on early liver virus accumulation was observed, suggesting no effect on Kupffer cell interactions. Hence, coagulation factors play a pivotal role in selectively mediating liver hepatocyte transduction of Ad5 and Ad5/47 vectors.
Waddington
Simon N
SN
Department of Haematology, Haemophilia Centre and Haemostasis Unit, Royal Free and University College Medical School, London NW3 2PF, United Kingdom.
Parker
Alan L
AL
Havenga
Menzo
M
Nicklin
Stuart A
SA
Buckley
Suzanne M K
SM
McVey
John H
JH
Baker
Andrew H
AH
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001779:Blood Coagulation Factors / Q000502:physiology*; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D017930:Genes, Reporter; D005822:Genetic Vectors; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000166:cytology / Q000821:virology; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D051379:Mice; D023421:Models, Animal; D011991:Receptors, Virus / Q000378:metabolism; D014161:Transduction, Genetic; D053585:Virus Attachment / Q000187:drug effects*; D014859:Warfarin / Q000494:pharmacology
D000925:Anticoagulants; D001779:Blood Coagulation Factors; C568772:CLMP protein, mouse; D036022:Capsid Proteins; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; C018315:hexon capsid protein, Adenovirus; D014859:Warfarin; D008156:Luciferases