Therapeutic proteins production in insect cells

Modern biopharmaceutical research and the development of new therapeutic solutions are most often based on the study of genes and the proteins they code for. The advent of high-throughput whole-genome sequencing technologies and the availability of the computing power needed to exploit the data generated have considerably strengthened the role of genetic engineering and molecular biology. As a result, the fundamental life mechanisms – of DNA transcription and messenger RNA translation – are exploited in a wide range of living systems to synthesize proteins for use in pharmaceutical development programs.

Whether for in vitro screening of chemical molecules, building cell models expressing a particular receptor, developing a therapeutic monoclonal antibody or a recombinant vaccine, recombinant protein production systems are the rule.

Among these systems, insect cells occupy an intermediate position between bacteria (prokaryotes) and unicellular eukaryotes (yeasts), on the one hand, and, on the other, higher mammalian cells such as CHO (Chinese Hamster Ovary cells). The Escherichia coli bacterium was the first production system developed for the production of a therapeutic protein, human insulin. Thanks to its ease of use, rapidity, production yields and low cost, this organism is often evaluated as a first-line treatment. However, the absence of important post-translational protein modifications, such as glycosylation, proteolytic maturation or the formation of certain disulfide bridges, often makes the use of eukaryotic systems indispensable, especially when genetic engineering cannot overcome the obstacles.

At the other end of the chain, mammalian cells (mainly CHO) are today the system of choice for producing complex therapeutic proteins. Monoclonal antibodies, of which some thirty have been approved and are on the market, are the prime example of complex multimeric proteins produced in these cells.

Insect cells are widely used to produce proteins for biopharmaceutical research. They are proving to be a highly attractive alternative for achieving the complex co- and post-translational modifications required for a large number of proteins, particularly human ones. Thanks to the baculovirus vector, they are quick to implement, and generally enable high production yields (from 100 mg to 1 g/L). This expression system also offers enhanced biological safety. The elements used do not present any pathogenic risk for vertebrates or plants.

Despite a number of drawbacks that are still holding back its large-scale development for pharmaceutical biomanufacturing, the baculovirus/insect cell system seems to have found its first field of predilection in vaccines. Indeed, several human and veterinary...