Expression Technologies

We know that increasing yield while keeping costs low is everyone’s goal. Beyond buying and mixing supplements, companies are turning to new technology breakthroughs that can significantly increase yield. In fact, technology now exists to produce proteins using bacterial, fungal and mammalian cells, and insect and plant cell systems are emerging. Most therapeutic proteins are complex, however, requiring modification following synthesis for appropriate biological activity, biodistribution and pharmacokinetics. Such modifications, for example the authentic glycosylation of antibodies, are essentially only provided by mammalian cells. It is largely for this reason that the great majority of protein therapeutics on the market is manufactured in mammalian cells. 60-70% of all recombinant protein therapeutics is produced in mammalian systems.

With this trend, an expansion of the commercial market for recombinant protein production from mammalian cells has required an improvement in the efficiency and stability of production. Sustained expression of the transgenes is required for most of these applications and this requires integration of the transgenes into the host cell chromosome.

Conventional technology for expression in mammalian cells is very inefficient because transgenes are silenced upon integration because they are usually incorporated into a highly condensed state (“closed chromatin” or heterochromatin) in which the transgene DNA is inaccessible to the gene expression (transcription) machinery of the cell. Most of the genome is in the form of closed chromatin. With virtually all vectors and approaches to gene delivery into cells, integration occurs in random positions in the genome, such that the great majority of integration-event is unproductive or gives low level, unstable expression due to transgene silencing. Given these challenges, companies are turning more and more to new technologies that help to overcome production obstacles.