Human Adenovirus Vectors for Gene Transfer into Mammalian Cells

Publisher The high efficiency of gene transfer mediated by recombinant Adenovirus (Ad) has prompted the construction of dozens of first-generation Ad vectors for high level transgene expression in mammalian cells. These vectors have been designed and employed for uses as diverse as recombinant protein production and characterization, transcriptional analysis, establishment of stably transformed cell lines, and gene therapy. As the Ad vector system holds such huge potential for expression of foreign DNA, particularly in gene therapy regimens, it has been the subject of intense research. This chapter summarizes the advances made in Ad vector design, as well as describes the current status of Ad vector applications for expression analysis and in gene therapy. Because of their ability to infect a wide range of cell types at high efficiencies, recombinant Ads have become powerful tools for the analysis of cis-acting elements involved in transcriptional regulation in different tissues or in response to different stimuli. The insertion of inducible promoters into Ad vectors has facilitated mapping of the various inducer-responsive elements in those promoters. Research on Ad vectors for their potential use in gene therapy has grown enormously. Some of the most encouraging applications of Ad vectors in gene therapy, such as the immunotherapy of cancer, require transient high-level expression of the transgene in target cells that is easily achieved with first-generation Ad vectors. Gene replacement therapies, however, require prolonged expression and/or repeated administration of the vector, both of which have been problematic owing to activation of the host immune system against Ad and Ad-infected cells. These difficulties are being addressed by the development of second-generation vectors and of strategies to modulate the host immune response. These improvements, and no doubt others yet to come, hold promise for the generation of genuinely effective vectors for treatment of genetic disorders and other diseases.