Crucell’s STAR® technology is useful for increasing production of recombinant antibodies and therapeutic proteins on mammalian cell lines. Currently, more than 90% of all antibodies and therapeutic proteins are produced on derivatives of Chinese hamster ovary cells (CHO-K1 and CHO-DG44). It is therefore important that the technology has been successfully used to increase yield in such cell lines.
All cells in a human body contain identical DNA, but different types of cells have distinct functions. This is a result of cellular differentiation. Cellular differentiation is driven by the microenvironment during development or regeneration of tissue, which determines what parts of the DNA are either active or repressed. The active or repressed state of the DNA, or so-called gene expression profile, determines which proteins are expressed by the cell and which not.
Each cell type has its own specific gene expression profile. In order to maintain its identity and function, it is important that the cell maintains its gene expression profile. Epigenetic gene regulation mechanisms play a pivotal role in maintaining the gene expression profile of a cell. Maintenance of gene expression is also important for expression of a gene of interest (antibody or therapeutic protein). However, due to these epigenetic gene regulation mechanisms often the expression of the gene of interest is lost. Crucell has identified DNA elements in the human genome that are able to counteract epigenetic gene repression. These elements are called STAR®-elements. By flanking a gene of interest with STAR®-elements, stable mammalian cell lines can be generated that demonstrate much higher expression of the gene of interest than without STAR®-elements. In this way higher yields of the protein of interest can be obtained.
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