Glycoengineering in CHO Cells: Advances in Systems Biology

Abstract

For several decades, glycoprotein biologics have been successfully produced from Chinese hamster ovary (CHO) cells. The therapeutic efficacy and potency of glycoprotein biologics are often dictated by their post-translational modifications, particularly glycosylation, which unlike protein synthesis, is a non-templated process. Consequently, both native and recombinant glycoprotein production generate heterogeneous mixtures containing variable amounts of different glycoforms. Stability, potency, plasma half-life, and immunogenicity of the glycoprotein biologic are directly influenced by the glycoforms. Recently, CHO cells have also been explored for production of therapeutic glycosaminoglycans (e.g., heparin), which presents similar challenges as producing glycoproteins biologics. Approaches to controlling heterogeneity in CHO cells and directing the biosynthetic process toward desired glycoforms are not well understood. A systems biology approach combining different technologies is needed for complete understanding of the molecular processes accounting for this variability and to open up new venues in cell line development. In this review, we describe several advances in genetic manipulation, modeling, and glycan and glycoprotein analysis that together will provide new strategies for glycoengineering of CHO cells with desired or enhanced glycosylation capabilities.

Multiplex secretome engineering enhances recombinant protein production and purity

“…The dramatically lowered HCP ppm values during purification of a mAb will facilitate downstream processes. These HCP-reduced knockouts can be combined with additional advantageous genetic modifications, such as the production of glycoengineered proteins [15][16][17][18] , higher viability during long culture times 19 , viral resistance or elimination [20][21][22] , and/or clones with higher protein production stability of mAbs 23 , to create predictable upstream and downstream processes with full control over critical process parameters.…”

Genetic engineering approaches to improve posttranslational modification of biopharmaceuticals in different production platforms

“…CHO N-glycan engineering, we refer to a recently published review (Tejwani, Andersen, Nam, & Sharfstein, 2018).…”

Over-Production of Therapeutic Growth Factors for Cartilage Regeneration by Protein Production Platforms and Protein Packaging Cell Lines: A Narrative Review of the Current State-of-the-Art

“…HEK-293 is a cell line derived from human embryonic kidney cells grown in tissue culture and is widely used in cell biology and biotechnology [27]. The cells were derived from human embryonic kidney but the phenotypic origin of the cells is thought to be CHO cells are used in diverse biological and medical research applications [28]. CHO cells are also used commercially for the production of clinically relevant therapeutic proteins.…”