ABSTRACT

Reporter gene assay technology arose in the mid-80’s as a by-product when the expression of foreign genes in recipient cells had become a reality (1–3). Since then, the use of reporter genes has become a standard tool in drug screening assays. New vectors and improved methods allow the design of a huge variety of assay systems for high throughput screens (HTS) today. A dozen different reporter genes can be used, each in combination with many different vectors to work in a number of appropriate recipient cells (4–6). However, some of them gained broader attention like ß-galactosidase (lacZ), chloramphenicol acetyltransferase (CAT) and Photinus pyralis luciferase (luc). With time, they have been improved by modifications for more convenient use. Newer developments used photoactive gene products like aequorin or GFP (green fluorescent protein) both proteins from the jelly fish Aequorea victoria (7, 8). Others have been made more sensitive by modified substrates like secreted alkaline phosphatase (SEAP) and β-glucuronidase (GUS) (9). The construction of sophisticated reporter vectors has been described in a number of review publications (5, 6, 10–12) and shall not be discussed here. This paper will focus more on the technological aspect of reporter gene assays. As reporter gene technology opens up fascinating possibilities to construct models for gene and metabolic regulation, as well as for receptor functions and cellular toxicology (13, 14), this relatively new field has been rapidly adopted by the drug screening community and is believed to be the most powerful technology in searching for substances interacting with well defined cellular targets. However, other applications like diagnostic screening (15) and plant biotechnology remain to be summarized elsewhere.