ABSTRACT

However, there are limitations to the use of bacteria for the production of proteins, espe­ cially of complex proteins from higher organisms. While the genetic code is universal, the machinery for protein processing is not and bacteria lack the enzymes and organelles, which, for example, in mammalian cells are responsible for further processing and modification of the proteins (e.g., glycosylation, disulfide bridge formation, cleavage). Especially in the case of larger proteins, bacteria are often not able to fold the amino acid chain into the correct three-dimensional structure required for “biological activity”. Last but not least, the tendency of bacteria to store produced proteins inside the cell in the form of denatured precipitates, so-called inclusion bodies, has been known to considerably reduce the yield of active protein. For this reason, mammalian cells, which have been adapted to propagation in single cell cul­ ture, are nowadays used to produce the more complex but also more valuable products of modern biotechnology. Well-known examples are the various CHO cell lines derived from Chinese hamster ovary cells.3 In order to enable such mammalian cells to produce a desiredhuman-protein, they too need to be genetically modified. The genetic manipulation of mam­ malian cells (“transfection”) is much more difficult than that of bacteria. Over the last years a

Synthetic Polymers f o r Biotechnology and M edicine, edited by Ruth Freitag.