Factors Affecting the Expression of Recombinant Protein and Improvement Strategies in Chinese Hamster Ovary Cells

Abstract

Recombinant therapeutic proteins (RTPs) are important parts of biopharmaceuticals. Chinese hamster ovary cells (CHO) have become the main cell hosts for the production of most RTPs approved for marketing because of their high-density suspension growth characteristics, and similar human post-translational modification patterns et al. In recent years, many studies have been performed on CHO cell expression systems, and the yields and quality of recombinant protein expression have been greatly improved. However, the expression levels of some proteins are still low or even difficult-to express in CHO cells. It is urgent further to increase the yields and to express successfully the "difficult-to express" protein in CHO cells. The process of recombinant protein expression of is a complex, involving multiple steps such as transcription, translation, folding processing and secretion. In addition, the inherent characteristics of molecular will also affect the production of protein. Here, we reviewed the factors affecting the expression of recombinant protein and improvement strategies in CHO cells.

Keywords: CHO; difficult to express; expression vector; recombinant protein; recombinant therapeutic proteins.

FIGURE 1

Process of protein synthesis. mRNA is transcribed in the nucleus, transported to the cytoplasm and translated by the ribosome, and then the protein binds to the rough endoplasmic reticulum, folding and processing before entering the Golgi apparatus. The soluble protein is PTMs and then secreted through the secretory pathway. Through cell engineering strategies such as anti-apoptotic engineering, metabolic engineering, cell cycle engineering, and protein PTMs engineering, overexpression of dominant genes, gene knockout, and siRNA interference inhibit unfavorable gene expression, transform mammalian cell lines, and improve cell lines Performance, effectively improve cell viability and increase the production of recombinant protein.