Efficient production of large variety of biologically active antibody fragments in Escherichia coli.

What is it about?

In this publication we show that bacterial cells can be employed as a very efficient factories for production of biologically active human proteins, such as antibody fragments.

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Why is it important?

Antibodies are proteins produced in large variety by the immune system; an antibody is able to recognize very precisely a target, e.g. a pathogen, and launch defense response. Antibodies have extraordinary properties that are desired for research, diagnostics and as therapeutic agents. They are very large and complex proteins, build of several domains that perform specific funcions; isolated domains retain their functions, therfore there is a strong interest in antibody fragments as well. Structure of an antibody is stabilized and bound together by covalent linkages called disulfide bonds; bacteria are not specialized for production of disulfide-bonded proteins and they target such proteins for final shaping to a very small compartment that constitutes less than 20 % of total cell volume. Our system is innovative, because it allows production of biologically active antibody fragments in the main bacterial cell compartment called cytoplasm that can accumulate large amounts of proteins. Up to date, antibodies and antibody fragments could be so efficiently produced only in mammalian cells, that are fragile and require sophisticated nutrients, thus are dificult, time consuming and expensive to cultivate. On the contrary, bacteria are relatively simple for genetic manipulations, grow very fast and require only very basic nutrients.