Purification of DNA production of drugs
15 Jan 2000
Zeneca LifeScience Molecules' Cambridge Research Biochemicals(CRB) and Pharmacia Bio-tech are jointly investigating process scale (bulk) purification of DNA-based therapeutic drugs, known as oligonucleotides.
Cheshire-based CRB will prepare the material and the purification scheme while Pharmacia, of Uppsala, Sweden, will provide the chromatography media, purification equipment and processes.
Mick McLean, DNA development technical manager at CRB, told PE: `The goal is to produce completely specific medicines, but a problem with the synthetic DNA process is that reactions don't always go to completion, so we get undesirable by-products.
`The sort of molecule we are talking about is 20 residues long, with a typical molecular weight of 6500-7000, which needs to be constructed by an iterative process.'
In order to obtain the resultant pure synthetic DNAcost effectively, CRB teamed up with Pharmacia to develop effective purification by a range of liquid chromatography methods.
The team also looked at making the molecules in separate sections, such as two pieces of 10 nucleotides [`N' in the diagram] to minimise contamination.
Typical targets for the drugs are cancer, viral diseases and inflammatory diseases.
The starting material is a nucleotide base, often obtained from fish sperm, but also from fermentation and bacterial synthesis. Yields obtained so far are confidential, but they have been `reasonable.'
The launch of commercial product is likely to be post 2000, although last year CRB produced 0.5kg of DNAfor US testing.
DNAis likely to be required in tonne quantities for commercial production of these medicines. Companies such as Novartis, Hoechst, Boehringer Ingelheim, and Glaxo Wellcome, have all invested in this area.
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