{
  "id": 10443342,
  "title": "Next-gen glycoengineering: combining cellular and metabolic engineering to fine tune mAb β1,4-galactosylation",
  "url": "https://urgent.news/2026/09/28/next-gen-glycoengineering-combining-cellular-and-metabolic",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-28T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.26.754714v1?rss=1"
  },
  "original_language": "en",
  "account": "Therapeutic monoclonal antibodies (mAbs) with N-linked Fc galactosylation exhibit variability in quality, impacting complement-dependent cytotoxicity and ADCC. Current control methods have limited ranges, causing productivity losses and unwanted glycoforms. Researchers have now combined metabolic and cellular glycoengineering techniques. By feeding 2-deoxy-2-fluorogalactose (2FG) to CHO cells engineered for hypergalactosylation via COSMC knockout and {beta}4-galactosyltransferase overexpression, they achieved broad, tunable control over Fc {beta}4-galactosylation. This method was tested in different cell lines, revealing that 2FG dosing does not translate across all lines. A new cell-normalised, multi-bolus feeding strategy was developed, which expanded control in certain cell lines while reducing aglycosylation and Man5 formation. This strategy, applied in a fed-batch Ambr(R) 250 process, reduced the amount of 2FG needed, showing its efficiency. Ultimately, Bio-Layer Interferometry identified Fc {beta}4-galactosylation as the strongest predictor of Fc{gamma}RIIIA (CD16a) binding affinity. These advancements pave the way for controlling mAb galactosylation across a wide range, potentially fine-tuning downstream pharmacological activity.",
  "summary": "N-linked Fc galactosylation drives variability in therapeutic mAb quality, affecting complement-dependent cytotoxicity and ADCC. Current control strategies suffer from narrow ranges, productivity loss, or unwanted glycoforms. Here, we combine metabolic and cellular glycoengineering by feeding 2-deoxy-2-fluorogalactose (2FG) to CHO cells engineered for hypergalactosylation via COSMC knockout and…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}