Crucell buys protein production firm
ChromaGenics in a move to get hold of a promising new technology
that could boost yields of proteins and antibodies made in cell
culture, writes Phil Taylor.
Using the STAR technology can hike production by three- to five-fold, improving the efficiency of biopharmaceutical production and potentially reducing the cost of making biologic drugs, according to Crucell.
Prof Arie Otte, who discovered STAR and founded ChromaGenics, told DrugResearcher.com that the technology is based on the concept of epigenetics - the study of cellular factors (usually DNA and protein factors) that are involved in the regulation of gene expression.
In man, 80 to 90 per cent of genes are switched off, or silenced, because they code for proteins that are not essential for the functioning of cells. In fact, genes are silenced by default in cells, and those that need to remain active only do so because of the action of regulatory sequences.
This means that when cells are transformed with the DNA sequence required to make a protein, "the chances that the gene is integrated into a silent part of the genome are large," commented Prof Otte. The solution is to use regulatory sequences - known as STAR elements - on either side of the protein-coding sequence (transgene), to create a non-silent portion of the genome.
Aside from improving protein expression, STAR elements have the additional benefit of improving the stability of the transgene, said Prof Otte.
This is probably the most important aspect of the technology, as it solves a fundamental problem in biopharmaceutical production - the reversion of transgenes to their silent state. At present, a significant proportion of cells in a typical bioreactor may not be producing the desired protein at all, he noted.
And in addition to its applications in protein expression, STAR could also help solve a major obstacle holding up the development of gene and cell therapies - the poor expression levels that occur when gene sequences are delivered to human cells in vivo.
Prof Otte stressed that there is still some development work to be done on the STAR technology, and he will be joining Crucell part time as Director of Epigenetics Technology, along with five other ChromaGenics staff who will be on full-time contracts, to help turn it into a commercial proposition. The terms of the acquisition have not been disclosed.
One issue will be to make sure that the technology will function in Crucell's PER.C6 cell line, which is fast becoming an industry standard in biopharmaceutical production with more than 30 licensees.
Jaap Goudsmit, chief scientific officer of Crucell, said that once fully-developed, STAR "will reduce the cost of industrial scale production of proteins and antibodies, to levels otherwise difficult to achieve."
The company is predicting that STAR will show a similar growth rate to PER.C6, and the acquisition adds another potential licensing revenue stream, which is becoming increasingly important given the successful penetration of PER.C6 into the biopharmaceutical production market.
This is penetration is also a factor in Crucell's recent decision to expand its activities into the in-house development of vaccines and antibodies that prevent and treat infectious diseases, including Ebola, influenza, malaria and West Nile virus.
