Document Detail


The vesicle-trafficking protein munc18b increases the secretory capacity of mammalian cells.
MedLine Citation:
PMID:  19723587     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heterologous protein production in mammalian cells is often challenged by the bottleneck of the secretory machinery, which prevents producer cells from fully exploiting their physiologic capacity in the production of biopharmaceuticals. Recent advances in the understanding of the molecular mechanisms of vesicle trafficking have enabled the identification of key regulators that control the flow of recombinant proteins along the secretory pathway. Here, we report that transgenic expression of Munc18b, a Sec1/Munc18 (SM) protein regulating the fusion of secretory vesicles to the plasma membrane, enhances the secretory capacity of HeLa, HEK-293 and HT-1080 and so increases overall production of different secreted human glycoproteins as well as the titer of lentiviral particles produced in HEK-293-derived helper cells. Targeted interventions in secretory vesicle trafficking by Munc18b is a novel secretion engineering strategy, which harnesses the full secretory capacity of mammalian cells. Secretion engineering is the latest-generation metabolic engineering strategy, which could improve future therapies by increasing the production of biopharmaceuticals by boosting the secretion performance of cell implants in cell therapy initiatives and by raising the production titers of transgenic viral particles used for gene therapy applications.
Authors:
Ren-Wang Peng; Claudio Guetg; Marcel Tigges; Martin Fussenegger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-31
Journal Detail:
Title:  Metabolic engineering     Volume:  12     ISSN:  1096-7184     ISO Abbreviation:  Metab. Eng.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-11-16     Completed Date:  2010-01-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815657     Medline TA:  Metab Eng     Country:  Belgium    
Other Details:
Languages:  eng     Pagination:  18-25     Citation Subset:  IM    
Affiliation:
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
CHO Cells
Cricetinae
Cricetulus
Gene Expression*
Hela Cells
Humans
Munc18 Proteins / biosynthesis*,  genetics
Protein Transport / physiology
Recombinant Proteins / biosynthesis*,  genetics
Secretory Vesicles / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Munc18 Proteins; 0/Recombinant Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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