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Published on: July 30, 2018
Recombinant adenovirus as a methodology for exploration of physiologic functions of growth factor pathways
Kevin Wei1, Frank Kuhnert, Calvin J Kuo
1Division of Hematology, Stanford University School of Medicine, 269 Campus Dr., CCSR 1155, Stanford, CA 94305, USA.
Abstract:
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.
Insights
Recombinant adenoviruses (Ad) enable potent in vivo inactivation of growth factor pathways. This powerful tool reveals novel physiological roles and therapeutic potential for signaling pathways in experimental models.
Area of Science:
- Molecular Biology
- Animal Models
- Physiology
Background:
- Growth factor pathways are crucial for physiological functions.
- Studying these pathways in vivo requires precise control over their activity.
- Recombinant adenoviruses offer a method for targeted pathway modulation.
Purpose of the Study:
- To review the use of recombinant adenoviruses (Ad) for inactivating growth factor pathways in vivo.
- To discuss the advantages and limitations of this approach.
- To highlight how Ad-mediated pathway inactivation can uncover novel physiological roles.
Main Methods:
- Utilizing recombinant adenoviruses to express secreted antagonists of growth factors.
- Administering a single adenoviral injection for persistent expression of antagonists.
- Inactivating specific growth factor pathways, such as vascular endothelial growth factor and Wnt systems, in experimental animals.
Main Results:
- Recombinant Ad achieve high-level, persistent plasma expression of antagonists.
- This allows for stringent, conditional inactivation of target pathways in vivo.
- Studies using vascular endothelial growth factor and Wnt pathways exemplify the discovery of previously unknown physiological roles.
Conclusions:
- Recombinant adenoviruses are a powerful strategy for studying growth factor pathway physiology in vivo.
- This method facilitates the discovery of novel physiological functions.
- Findings have potential implications for both physiological understanding and therapeutic development.
