CRISPR-Cas9 Genome Editing Tool for the Production of Industrial Biopharmaceuticals

Mol Biotechnol. 2020 Sep;62(9):401-411. doi: 10.1007/s12033-020-00265-9. Epub 2020 Aug 4.

Abstract

A broad range of cell lines with characteristic features are used as bio-factories to produce recombinant proteins for basic research and therapeutic purposes. Genetic engineering strategies have been used to manipulate the genome of mammalian cells, insects, and yeasts for heterologous expression. One reason is that the glycosylation pattern of the expression hosts differs somehow from mammalian cells, which may cause immunogenic reactions upon administration in humans. CRISPR-Cas9 is a simple, efficient, and versatile genome engineering tool that can be programmed to precisely make double-stranded breaks at the desired loci. Compared to the classical genome editing methods, a CRISPR-Cas9 system is an ideal tool, providing the opportunity to integrate or delete genes from the target organisms. Besides broadened applications, limited studies have used CRISPR-Cas9 for editing the endogenous pathways in expression systems for biopharmaceutical applications. In the present review, we discuss the use of CRISPR-Cas9 in expression systems to improve host cell lines, increase product yield, and humanize glycosylation pathways by targeting intrinsic genes.

Keywords: CRISPR-Cas9; Expression systems; Genome editing; Glycoengineering; Humanizing glycosylation; Therapeutic glycoproteins.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Products*
  • CRISPR-Cas Systems*
  • Cell Line
  • Gene Editing*
  • Insecta
  • Mammals
  • Yeasts

Substances

  • Biological Products