ArticleNature metabolism2025
Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Highly multiplexed mammalian metabolic engineering with a shotgun approach.Nature biotechnology · 2026Article
- Nicotinamide Reverses the Warburg Effect in CHO Cell Culture.Biotechnology and bioengineering · 2026Article
- A community reconstruction of Chinese hamster metabolism and structural systems biology elucidate metabolic rewiring in lactate-free CHO cells.Cell systems · 2026Article
- Delineating the Transcriptional and Phenotypic Impact from Biotherapeutic Glycoengineering.bioRxiv : the preprint server for biology · 2026Article
- Genetic drivers of Chinese hamster ovary cell proliferation revealed by functional genomics.iScience · 2025Article
- Elastic Cytomatrix Dynamics Influences Metabolic Rate and Tumor Microenvironment Formation.Cancers · 2025Review
- H2BC9 lactylation modulates esophageal squamous cell carcinoma progression via the Wnt/β-catenin signaling pathway.Journal of translational medicine · 2025Article
- Cytoplasmic physicochemical factors drive malignant transformation by adapting bioenergetic settings.Biochemistry and biophysics reports · 2025Article
- Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer.Cells · 2025Review
- The Warburg hypothesis and the emergence of the mitochondrial metabolic theory of cancer.Journal of bioenergetics and biomembranes · 2025Review
- Wheels turning: CHO cell modeling moves into a digital biomanufacturing era: Subtitle: CHO Metabolic Modeling.Computational and structural biotechnology journal · 2025Review
- Sequential, chromosome-specific glutamine synthetase double knockout with Cas-CLOVER establishes enhanced CHO platforms for cell line development.Biotechnology progressArticle
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Abstract
The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA. These cells, which we refer to as Warburg-null cells, maintain wild-type growth rates while producing negligible lactate, show a compensatory increase in oxygen consumption, near total reliance on oxidative metabolism, and higher cell densities in fed-batch cell culture. Warburg-null cells remain amenable for production of diverse biotherapeutic proteins, reaching industrially relevant titres and maintaining product glycosylation. The ability to eliminate lactate production may be useful for biotherapeutic production and provides a tool for investigating a common metabolic phenomenon.
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