ArticlePloS one2012
Chemical chaperones improve protein secretion and rescue mutant factor VIII in mice with hemophilia A.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 45 citations in OpenAlex.
- An integrated cell and medium engineering approach for production of a nanobody fusion in Saccharomyces cerevisiae.Applied microbiology and biotechnology · 2026Article
- OsmoFold: A high-throughput tool for predicting the impact of osmolytes on protein structure.Biophysical journal · 2025Article
- Functional Activities of Cohesin Proteins Can Be Altered by Chemical Chaperones.The protein journal · 2025Article
- Cell-Based Small-Molecule Screening Identifying Proteostasis Regulators Enhancing Factor VIII Missense Mutant Secretion.Biomolecules · 2025Article
- Impact of SARS-CoV-2 RBD Mutations on the Production of a Recombinant RBD Fusion Protein in Mammalian Cells.Biomolecules · 2022Article
- Defects in Protein Folding and/or Quality Control Cause Protein Aggregation in the Endoplasmic Reticulum.Progress in molecular and subcellular biology · 2021Article
- Molecular Mechanisms and Determinants of Innovative Correction Approaches in Coagulation Factor Deficiencies.International journal of molecular sciences · 2019Review
- The effect of the chemical chaperone 4-phenylbutyrate on secretion and activity of the p.Q160R missense variant of coagulation factor FVII.Cell & bioscience · 2019Article
- A protein chimera strategy supports production of a model "difficult-to-express" recombinant target.FEBS letters · 2018Article
- Synergistic Inhibition of Protein Fibrillation by Proline and Sorbitol: Biophysical Investigations.PloS one · 2016Article
- Gene therapy for hemophilia.Frontiers in bioscience (Landmark edition) · 2015Review
- A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia.PLoS genetics · 2014Article
- SLC30A10 is a cell surface-localized manganese efflux transporter, and parkinsonism-causing mutations block its intracellular trafficking and efflux activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Innovative strategies to treat protein misfolding in inborn errors of metabolism: pharmacological chaperones and proteostasis regulators.Journal of inherited metabolic disease · 2014Review
- The F309S mutation increases factor VIII secretion in human cell line.Revista brasileira de hematologia e hemoterapiaArticle
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inefficient intracellular protein trafficking is a critical issue in the pathogenesis of a variety of diseases and in recombinant protein production. Here we investigated the trafficking of factor VIII (FVIII), which is affected in the coagulation disorder hemophilia A. We hypothesized that chemical chaperones may be useful to enhance folding and processing of FVIII in recombinant protein production, and as a therapeutic approach in patients with impaired FVIII secretion. A tagged B-domain-deleted version of human FVIII was expressed in cultured Chinese Hamster Ovary cells to mimic the industrial production of this important protein. Of several chemical chaperones tested, the addition of betaine resulted in increased secretion of FVIII, by increasing solubility of intracellular FVIII aggregates and improving transport from endoplasmic reticulum to Golgi. Similar results were obtained in experiments monitoring recombinant full-length FVIII. Oral betaine administration also increased FVIII and factor IX (FIX) plasma levels in FVIII or FIX knockout mice following gene transfer. Moreover, in vitro and in vivo applications of betaine were also able to rescue a trafficking-defective FVIII mutant (FVIIIQ305P). We conclude that chemical chaperones such as betaine might represent a useful treatment concept for hemophilia and other diseases caused by deficient intracellular protein trafficking.
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