Rapid Antibody Glycoengineering in CHO Cells Via RNA Interference and CGE-LIF N-Glycomics

Methods Mol Biol. 2022:2370:147-167. doi: 10.1007/978-1-0716-1685-7_7.

Abstract

The impact of the glycan distribution on the in vivo function and half-life of monoclonal antibodies has long motivated the genetic engineering of producer cells to achieve structures that enhance efficacy, safety and stability. To facilitate glycoengineering of IgG-producing Chinese hamster ovary cells, we present a rapid protocol that involves the use of RNA interference for the knockdown of genes of interest coupled with capillary gel electrophoresis and laser-induced fluorescence detection (CGE-LIF) for fast, high-throughput glycan analysis. We apply this methodology to the Fut8 gene, responsible for the addition of core fucose, which is a typical target for increasing antibody-dependent cellular cytotoxicity.

Keywords: Antibody-dependent cell cytotoxicity; Capillary gel electrophoresis; Chinese hamster ovary cells; Fucosylation; Gene knockdown; RNAi; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Electrophoresis, Capillary
  • Glycomics*
  • Polysaccharides
  • RNA Interference

Substances

  • Antibodies, Monoclonal
  • Polysaccharides