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Suppression of programmed cell death in industrial scale biological production systems

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"Immortal" cells boost pharmaceutical production

The use of mammalian cell cultures for the production of biopharmaceuticals and other biological products is gaining worldwide acceptance as biotechnology paves the way for novel applications. However, the practice is hampered by lower-than-possible productivity attributed to specific cellular characteristics.

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One of these characteristics, is the genetically determined mechanism of programmed cell death, known as apoptosis. Apoptosis leads to the elimination of the cell in an ordered manner and is a key process involved in the balance of tissues. Within a cell culture setting, however, cell death results in a decrease of 'production units' and can have a serious effect of final yields. The EU's APOPTOSIS project set out to develop novel cell lines incorporating genes that could suppress the apoptotic pathway and hence prolong cell life. The main achievement of the project was the creation of a novel cell line transfected with the bcl-2 gene. The gene product carries the property to suppress apoptosis by preventing a key mechanism at the onset of the process. Studies showed that the over-expression of bcl-2 lead to specific improvements such as prolonged growth phase and higher maximum cell density. The bcl-2 transfected cell line yielded higher levels of end product (in this case an antibody) compared to the control cell line, not transfected with the gene. These findings could have important implications on the use of mammalian cell culture systems for the production of biopharmaceuticals and therefore pose special interest to pharmaceutical and biotechnology companies.

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