Tuesday, June 15, 2010

Understanding the impact of molecular biology on everyday life

The impact of molecular biology on everyday life has increased enormously over the last two decades. Medical, pharmaceutical and lately even agricultural applications of “gene technology” have become standard, if sometimes controversially viewed procedures. The feasibility of this “revolution” is based on a few biological facts; most importantly the relationship between DNA, RNA and proteins. DNA carries the information for protein production.

Basic units of information are called genes, which typically are DNA sequences of about 1500 base pairs (bp). Usually, one gene carries the information for one protein. While the proteins are highly specific to a species, the genetic code is universal and shared among all living organisms. Therefore, if a human gene is transferred into a bacterium, the bacterium will be able to translate this DNA sequence into the “correct”, i.e., human, amino acid sequence (protein). The insertion of foreign genes into bacteria has become a routine laboratory procedure1 and genetically modified bacteria have been widely used to produce so-called “recombinant” proteins for the pharmaceutical industry. A well-known example is the production of human insulin in E. coli.

However, there are limitations to the use of bacteria for the production of proteins, especially 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 culture, 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. In order to enable such mammalian cells to produce a desired – human - protein, they too need to be genetically modified. The genetic manipulation of mammalian cells (“transfection”) is much more difficult than that of bacteria. Over the last years a number of transfection strategies have been developed, amongst the methods that utilize (semi-) synthetic polymers. A controllable and successful transfection strategy is not only the basis for the production of recombinant proteins, but even more so for gene therapy. Considerable attention has therefore been paid to the development of synthetic polymers as vehicles for gene delivery. This chapter will focus on the current state of knowledge in regard to the requirements for putative transfection vehicles, but also will summarize and compare the various applications of such systems.

Tags: Bio Technology, Bio Genetics, Organ Rejection

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