4 Structure and Genetic Organization of Adenovirus Vectors

Abstract

Adenovirus (Ad) was first isolated in 1953 (Rowe et al. 1953) and not long after was recognized as an invaluable tool for the investigation of various aspects of mammalian molecular biology from oncogenesis to DNA replication, transcriptional regulation, and protein synthesis. Some of the features that made Ad preferable over other viruses for such studies include the ease with which the Ad genome can be experimentally manipulated, the ability to propagate Ad to high titer, and the efficiency with which Ad infects a wide variety of both quiescent and proliferating cells of various species and cell types. These properties have also made Ad an attractive vehicle for gene transfer and transgene expression in mammalian cells with numerous recent applications of Ad as a vector for human gene therapy (for review, see Bramson et al. 1995; Hitt et al. 1996; and this volume). This chapter overviews the structure and lytic cycle of wild-type Ad as well as the structure of first generation, second generation, and helper-dependent Ad vectors designed for gene therapy.

GENOMIC ORGANIZATION AND VIRION STRUCTURE
Adenoviruses have been isolated from many different avian and mammalian species, although the human Ads have been the most extensively studied. The approximately 50 known serotypes of human Ad have been divided into 6 subgroups based on immunological, biological, and DNA sequence similarities. The best characterized serotypes are adenovirus type 2 (Ad2) and Ad5 of subgroup C, Ad12 of subgroup A and Ad7 of subgroup B. However, all human Ads examined thus far share...