BioWorld International Correspondent

Crucell NV scooped up a smaller compatriot, ChromaGenics BV, for a down payment of €4 million, plus undisclosed earn-out provisions based on the attainment of future revenue milestones.

The deal gives Leiden, the Netherlands-based Crucell access to an epigenetic technology platform that could boost both the yield and the stability of transgenic protein-production systems.

Crucell aims to combine Amsterdam-based ChromaGenics' Stabilizing and Anti-repressor (STAR) genetic elements technology with its own recombinant protein expression system, PER.C6, which has more than 30 licensees. It also will make the platform available on a stand-alone basis.

"Anyone who is interested in producing large-scale proteins and antibodies could potentially be interested in licensing the STAR technology," Crucell spokeswoman Elizabeth Goodwin told BioWorld International.

The STAR technology is derived from a series of noncoding genetic elements - identified by ChromaGenics co-founder Arie Otte - which appear to play a role in the regulation of gene expression by influencing the accessibility of chromatin. Expression of transgenic DNA is poor if the introduced construct integrates into a host chromosome at or close to inaccessible chromatin, as the cell's transcription machinery is unable to gain access to the DNA.

Otte, who is a professor of biochemistry at the University of Amsterdam, and his co-workers reported in the May 2003 issue of Nature Biotechnology on a series of genetic elements that blocked the silencing effect when cloned upstream from a reporter construct and resulted in stabilized expression over a prolonged period. The precise molecular mechanism of the elements is not yet understood, he told BioWorld International, but they appear capable of blocking a range of chromatin-associated repressors, thereby boosting protein production.

"Dependent on the strength of the promoter, we are in the range of two- to fourfold yield improvements," he said.

None of the elements Otte's team identified exceeded 2,100 base pairs, and all but one worked in both human and chinese hamster ovary cells, indicating a potential applicability to recombinant protein production. It will take at least a year before the STAR technology will be scaled up for deployment in production settings.

"We need to [carry out] further development before we can exploit it from a licensing perspective. That could take quite a while," Goodwin said.

ChromaGenics was established as a spin-out from the University of Amsterdam in 2000. Five employees will transfer to Crucell, while Otte is taking up a part-time post with Crucell as director of epigenetics technology.

In separate news, Crucell reported Tuesday that NeoTropiX Inc., of Gaithersburg, Md., licensed PER.C6 for use in the research and clinical development of viral therapeutics for oncology indications, while ML Laboratories plc, of Warrington, UK, renewed its license for the technology for gene therapy applications.