The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line

TLDR

Chinese hamster ovary (CHO)-derived cell lines are the preferred host cells for therapeutic protein production. The study presents a draft genome sequence of the CHO‑K1 cell line, investigates glycosylation and viral susceptibility genes, and discusses how this resource can enable genome‑scale optimization of biopharmaceutical production. Scaffolds were mapped to 21 microfluidics‑isolated chromosomes to locate genes, and the authors examined glycosylation and viral entry genes to assess their expression and impact on protein quality and viral resistance. The 2.45‑Gb assembly contains 24,383 predicted genes; most human glycosylation‑associated genes are present but 141 are not expressed, and many viral entry genes are present but silent, potentially explaining CHO’s viral resistance.

Abstract

Chinese hamster ovary (CHO)-derived cell lines are the preferred host cells for the production of therapeutic proteins. Here we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45 Gb of genomic sequence, with 24,383 predicted genes. We associate most of the assembled scaffolds with 21 chromosomes isolated by microfluidics to identify chromosomal locations of genes. Furthermore, we investigate genes involved in glycosylation, which affect therapeutic protein quality, and viral susceptibility genes, which are relevant to cell engineering and regulatory concerns. Homologs of most human glycosylation-associated genes are present in the CHO-K1 genome, although 141 of these homologs are not expressed under exponential growth conditions. Many important viral entry genes are also present in the genome but not expressed, which may explain the unusual viral resistance property of CHO cell lines. We discuss how the availability of this genome sequence may facilitate genome-scale science for the optimization of biopharmaceutical protein production.