Towards a cleaner CHO chassis: systematic knockout of host cell proteins for efficient biopharmaceutical manufacturing.

ABSTRACT: Host cell proteins (HCPs) are major process-related impurities in biopharmaceutical manufacturing, imposing metabolic burden on production hosts and complicating downstream purification, thereby impacting cost, product stability, and patient safety. Here, we engineered Chinese hamster ovary (CHO) cells toward a streamlined production chassis through multiplex CRISPR-mediated knockout of abundant and difficult-to-remove HCPs. Proteomic profiling across multiple clones, products, and downstream purification steps identified a core set of highly abundant proteins that contributed disproportionately to total released HCP mass and showed limited removal by standard purification processes. Screening of 62 candidate genes using pooled and single-cell knockout approaches identified targets compati

SUBMITTER: Marzluf JP 

PROVIDER: S-EPMC12902299 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature