Use of Adenovirus-Mediated Gene Transfer to Facilitate Biological Annotation of Novel Genes

Abstract

As part of a large program of gene annotation, use of adenovirus-mediated gene transfer facilitated rapid progress in the functional evaluation of more than 100 genes. Localized or systemic exposure to gene products expressed by adenovirus-transduced cells led to the discovery of several novel activities through analysis of resulting physiochemical or histological changes. In this summary of the work, we present examples of two studies in which activities of novel growth factors were initially characterized using this approach. In the first example, intravenous delivery of adenovirus encoding different forms of platelet-derived growth factor (PDGF) allowed us to evaluate effects of systemic exposure to two new members of this family, PDGF-C and PDGF-D, and led to specific new hypotheses regarding their roles in diseases of the liver and kidney, respectively. In the second example, localized delivery of adenovirus encoding fibroblast growth factor (FGF)-18 to mouse pinna led to the discovery that this novel FGF is a trophic factor for mature chondrocytes and their progenitors and might be useful for treating cartilage disease. These examples serve to illustrate the potential of in vivo gene delivery approaches to facilitate functional analysis and focus of secondary investigation in a large screening effort.