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 encode. The advent of high-throughput whole-genome sequencing technologies and the availability of the computing power needed to analyze the resulting data have significantly strengthened the role of genetic engineering. As a result, the fundamental mechanisms of life – —namely DNA transcription and the subsequent translation of messenger RNAs – —are being harnessed in a wide range of living systems to synthesize proteins for use in pharmaceutical development programs.

Whether it is to perform in vitro screening tests on chemical compounds, to construct cell models expressing a specific receptor, to develop a therapeutic monoclonal antibody, or to create a recombinant vaccine, the use of a recombinant protein production system is almost always the norm.

Among these systems, insect cells occupy an intermediate position between bacteria (prokaryotes) and single-celled eukaryotes (yeasts), on the one hand, and the cells of higher mammals, such as CHO (Chinese Hamster Ovary) cells, on the other. The bacterium Escherichia coli was the first system developed for the production of a therapeutic protein, human insulin. Because it is simple to use and inexpensive, this organism is very often evaluated as a first-line option. However, the absence of significant post-translational protein modifications, such as glycosylation, often makes it necessary to use eukaryotic systems.

At the other end of the spectrum, mammalian cells (primarily CHO cells) are now the system of choice for producing complex therapeutic proteins. Monoclonal antibodies—of which well over a hundred have been approved and brought to 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 have emerged as a highly promising alternative for carrying out the complex co- and post-translational modifications required for a large number of proteins, particularly human proteins. Thanks to the baculovirus vector, this system is quick to set up and typically yields high production yields (ranging from 100 mg to 1 g/L). This expression system also offers enhanced biosafety. The components used in this system pose no pathogenic risk to either vertebrates or plants.

Despite a few drawbacks that hinder its large-scale development for pharmaceutical bioproduction, the baculovirus/insect cell system has found its first area of application in vaccines. Several vaccines—both human and veterinary—produced using this system are currently on the market. Robust procedures for insect cell culture...