By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Researchers detail new data in Metabolism. According to news reporting from Minneapolis, Minnesota, by NewsRx journalists, research stated, "Biopharmaceuticals derived from enveloped virus comprise an expanding market of vaccines, oncolytic vectors and gene therapy products. Thus, increased attention is given to the development of robust high titer cell hosts for their manufacture."
The news correspondents obtained a quote from the research from the University of Minnesota, "However, the knowledge on the physiological constraints modulating virus production is still scarce and the use of integrated strategies to improve hosts productivity and upstream bioprocess an under explored territory. In this work, we conducted a functional genomics study, including the transcriptional profiling and central carbon metabolism analysis, following the metabolic changes in the transition 'parental-to-producer' of two human cell lines producing recombinant retrovirus. Results were gathered into three comprehensive metabolic maps, providing a broad and integrated overview of gene expression changes for both cell lines. Eight pathways were identified to be recruited in the virus production state: amino acid catabolism, carbohydrate catabolism and integration of the energy metabolism, nucleotide metabolism, glutathione metabolism, pentose phosphate pathway, polyamines biosynthesis and lipid metabolism. Their ability to modulate viral titers was experimentally challenged, leading to improved specific productivities of recombinant retrovirus up to 6-fold. Within recruited pathways in the virus production state, we sought for metabolic engineering gene targets in the low producing phenotypes. A mining strategy was used alternative to the traditional approach 'high vs low producer' clonal comparison. Instead, 'high vs. low producer' from different genetic backgrounds (i.e. cell origins) were compared. Several genes were identified as limiting in the low-production phenotype, including two enzymes from cholesterol biosynthesis, two enzymes from glutathione biosynthesis and the regulatory machinery of polyamines biosynthesis."
According to the news reporters, the research concluded: "This is thus a frontier work, bridging fundamentals to technological research and contributing to enlarge our understanding of enveloped virus production dynamics in mammalian cell hosts."
For more information on this research see: Metabolic pathways recruited in the production of a recombinant enveloped virus: Mining targets for process and cell engineering. Metabolic Engineering, 2013;20():131-145. Metabolic Engineering can be contacted at: Academic Press Inc Elsevier Science, 525 B St, Ste 1900, San Diego, CA 92101-4495, USA. (Elsevier - www.elsevier.com; Metabolic Engineering - www.elsevier.com/wps/product/cws_home/622913)
Our news journalists report that additional information may be obtained by contacting A.F. Rodrigues, University of Minnesota, Dept. of Chem Engn & Mat Sci, Minneapolis, MN 55455, United States. Additional authors for this research include A.S. Formas-Oliveira, V.S. Bandeira, P.M. Alves, W.S. Hu and A.S. Coroadinha (see also Metabolism).
Keywords for this news article include: Biotechnology, Viruses, Virology, Minnesota, Metabolism, Minneapolis, Gene Therapy, United States, Bioengineering, Metabolic Engineering, North and Central America
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