Genome Editing for Cell-Line Development
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At BPI Europe in April 2019, Dirk Gewert (business unit leader of bioproduction at Horizon Discovery) told BioProcess Insider that Chinese hamster ovary (CHO) cell lines haven’t changed much in the 30 years since they were first used in biomanufacturing (1). Only a few companies offered commercially available, production-ready CHO cell lines for large-scale manufacturing of biotherapeutics. “In all cases,” he said, “cell lines were selected by identifying high-expressing clones and focusing on process optimization to improve expression and other critical quality attributes.”
Gewart’s company launched a consortium of suppliers to improve that situation. Its key objective was “to leverage modern gene-editing tools to improve the biology at the heart of the cell, ultimately to generate a fundamentally improved CHO expression platform available to the entire industry for the manufacturing of routine biotherapeutics.” Using genome-editing tools such as clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9), the company is developing “a suite of engineered cell lines optimized with different attributes for more challenging molecules.”
By 2020, industry consultant Dan Piestun could report on impressive progress — both within and beyond the CHO consortium’s — in the pages of BPI (2). He described how gene editing is being used across the biopharmaceutical industry for
• therapeutic protein expression regulation with smart promoters and epigenomic reprogramming.
• epigenetic control of therapeutic proteins.
• protein folding and secretion of recombinant cells.
• control of posttranslational modifications.
And just this year, a team of authors from Merck expanded on the latter application (3). They described a number of successful applications of genetic engineering methods for control of both N- and O-glycosylation as well as tyrosine sulfation and other modifications in mammalian cells.
Figure 1: