Recombinant pharmaceuticals from microbial cells: a 2015 update

Abstract

Diabetes, growth or clotting disorders are among the spectrum of human diseases related to protein absence or malfunction. Since these pathologies cannot be yet regularly treated by gene therapy, the administration of functional proteins produced ex vivo is required. As both protein extraction from natural producers and chemical synthesis undergo inherent constraints that limit regular large-scale production, recombinant DNA technologies have rapidly become a choice for therapeutic protein production. The spectrum of organisms exploited as recombinant cell factories has expanded from the early predominating Escherichia coli to alternative bacteria, yeasts, insect cells and especially mammalian cells, which benefit from metabolic and protein processing pathways similar to those in human cells. Up to date, around 650 protein drugs have been worldwide approved, among which about 400 are obtained by recombinant technologies. Other 1300 recombinant pharmaceuticals are under development, with a clear tendency towards engineered versions with improved performance and new functionalities regarding the conventional, plain protein species. This trend is exemplified by the examination of the contemporary protein-based drugs developed for cancer treatment.

Fig. 1

Number of recombinant protein products approved for use as drugs in humans, depending on the type of production platform

Fig. 2

Workflow involved in the development of a new drugs and approximate percentage (bars and numbers) of recombinant proteins currently in each step [9]

Fig. 3

Amount of marketed recombinant proteins (expressed in percentages) applied to each therapeutic area. Coloured in pink, other therapeutic areas (<5 % each) include diseases related to cardiology, central nervous system, ophthalmology and dermatology among others

Fig. 4

Cell factories used for the production of recombinant biopharmaceuticals against cancer (expressed in percentages)

Fig. 5

Schematic molecular structure of two marketed recombinant biopharmaceuticals

Fig. 6

Income provided by recombinant (top) and chemical drugs (bottom) against cancer in 2013. Figures according to Global Data [9]