Recombinant adenovirus as a methodology for exploration of physiologic functions of growth factor pathways.
The use of recombinant adenoviruses (Ad) to express secreted antagonists of growth factors represents a powerful strategy for studying physiologic functions of growth factor pathways in experimental animals. Indeed, a single adenoviral injection can produce characteristic high-level and persistent plasma expression of soluble receptor ectodomains or secreted protein antagonists, allowing highly stringent conditional inactivation of target pathways in vivo. In this review, we describe our experience using recombinant Ad to inactivate growth factor pathways in vivo and discuss their advantages and limitations. Using our studies on vascular endothelial growth factor and Wnt systems as examples, we further describe how recombinant Ad can unveil previously unknown physiological roles of signaling pathways. Finally, we discuss the potential physiological and therapeutic relevance of our findings.
Wei
Kevin
K
Division of Hematology, Stanford University School of Medicine, 269 Campus Dr., CCSR 1155, Stanford, CA 94305, USA.
Kuhnert
Frank
F
Kuo
Calvin J
CJ
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004274:DNA, Recombinant; D004920:Erythropoiesis / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
D004274:DNA, Recombinant; D036341:Intercellular Signaling Peptides and Proteins; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D051153:Wnt Proteins; D040262:Receptors, Vascular Endothelial Growth Factor