STAR® technology boosts protein yields

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 STAR® technology has been shown to significantly increase yields 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 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 are 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 this 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 expressing genes of interest (such as those carrying the code for an antibody or therapeutic protein). However, the cell’s epigenetic gene regulation mechanisms often block expression of the gene of interest.

Crucell has identified DNA elements in the human genome that are able to counteract epigenetic gene repression. These elements are called STAR® elements. Flanking a gene of interest with STAR® elements enables the generation of stable mammalian cell lines with much higher expression of the gene of interest than can be achieved without STAR®-elements. This leads to higher yields of the protein of interest.
 

 

A powerful combination

STAR® technology is a unique two-component system consisting of:
• STAR® elements that counteract gene silencing, resulting in increased levels of production and improved stability of recombinant proteins;
• STAR®-Select, a novel and very stringent selection system that is directly coupled to the expression of a gene of interest, resulting in only a few cell lines that all produce the recombinant protein at high levels.

 

The combination of STAR® elements and STAR®-Select results in significant reductions in both timelines and resources in cell clone generation programs.

Availability

Plasmids containing both STAR®-Select and STAR® elements have been generated. The therapeutic protein of interest, or both heavy and light chains of antibodies, can be inserted between STAR® elements. Customers can clone the gene of interest into the plasmids themselves or they can request this service from Crucell.