Therapeutic Applications of Transgenic Animals

Abstract

A transgenic organism carries additional genetic information in its genome (1). These added genes, the transgenes, are typically introduced into the genome when the organism is unicellular, i.e., in the single-celled zygote. As the cells divide and the embryo develops into a fetus, all cells inherit the transgene. Therefore, in the typical newborn transgenic animal, the transgene is present in all tissues. In real practice, many transgenic animals carry the transgene only in a sub-set of their total cellular composition, and are known as ‘mosaic’ for the transgene. This is due to the integration of the transgenes in the animal genome subsequent to the division of the unicellular zygote. Such mosaic animals, upon further breeding, can yield progeny where all cells carry the transgene. The expression of the transgene can be regulated by the choice of genetic control elements such as promoters, enhancers and locus control regions (LCRs). In theory, the design of the transgene should permit expression of the gene in one, selected, or all tissues of the animal. Similarly it is possible to impose developmental and spatial restriction on the expression of the transgene. Major advances in the understanding of gene regulation, especially the role of super-control elements, have contributed to the design of expression vectors which direct predictable levels and patterns of expression in transgenic animals. The ability of regulating gene expression in transgenic animals has opened the doors to the application of this technology to many areas of pharmaceutical endeavor (Table 1). This review summarizes three areas of utility for this technology that are currently of interest to DNX.