ABSTRACT
Animal cell culture has gained a paramount position in modern biotechnology, as evidenced by the large market share and important applications that proteins derived from this technology have in therapy, prophylaxis, and diagnosis. In fact, at least 16 recombinant proteins (r-proteins) derived from cell cultures, which account for about half of the r-DNA products approved to date, have reached the market (1). Furthermore, over 100 proteins produced from animal cell culture are presently undergoing clinical trials, and it is expected that more than half of the new protein drugs will require animal cells for their production. Gene expression in animal cells is required since the in vivo activity of many r-proteins strongly depends on complex posttranslational modifications that can only be performed by higher eukaryotic cells (2). In particular, mammalian cells are preferred for human applications since posttranslational modifications are closer to those found in human proteins. Mammalian cell culture technology has evolved significantly during the last 20 years; however, it still faces important challenges. For instance, transfection, selection, and amplification of stable and high-producing cell lines can be a laborious and timeconsuming task. Furthermore, product concentrations and productivities are in general lower, whereas overall bioprocessing costs are usually higher than for other expression systems, such as prokaryotes, lower eukaryotes, and transgenic plants and animals. Accordingly, there exists a permanent interest in better expression systems with the advantages of mammalian cell cultures but without their drawbacks. Among the various options, the insect cell-baculovirus expression vector system (IC-BEVS) represents a promising alternative.
