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Establishment of a production platform for recombinant therapeutic proteins in human cells


The main advantage of using mammalian cells as expression system consists in the fact that these cells are capable of performing post translational modifications as well as protein folding in an authentic way, thus generating a protein with correct therapeutic quality. Nevertheless, a major limitation of using this technology is the high cost of production due, for example, low expression levels and the need for complex and expensive culture media. Therefore, to have an economically viable production process some points should be carefully analyzed in the choice of the production system. The cell must be able to produce recombinant protein with the correct quality and at the highest possible levels and must be robust enough to allow the cultivation in bioreactors similar to those used on commercial scale. In addition, the culture medium selected must be capable of supporting the growth and the protein production at high levels at the lowest possible cost, with a composition that facilitates "downstream" steps. Human cell lines have attracted great interest since they are capable of producing glycosylated proteins in a more similar way to native human proteins. However, due to the recent application, these cells have not been properly characterized in terms of a future commercial application. Based on this, the main objective of this project is to establish a production platform for recombinant therapeutic protein using promising human cells evaluating the susceptibility of these cells to the scalable culture conditions and the potential for production of recombinant proteins. For this purpose, the human cell lines HKB-11, HepG2 and Sk-Hep, originally maintained in adhesion culture improving serum-containing medium, will be adapted for serum-free suspension cultures, using commercial or proprietary formulations, and evaluated in terms of the characteristics of growth, metabolism and susceptibility to scale-up through the cultivation in bioreactors. The potential for production of recombinant proteins will be assessed, in the cells that have presented the most promising characteristics, through the transient transfection technology using lentiviral vectors carrying genes for the expression of factors VIII and IX of coagulation. (AU)

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Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SWIECH, KAMILLA; PICANCO-CASTRO, VIRGINIA; COVAS, DIMAS TADEU. Production of recombinant coagulation factors: Are humans the best host cells?. BIOENGINEERED, v. 8, n. 5, p. 462-470, 2017. Web of Science Citations: 4.
BOMFIM, ALINE DE SOUSA; CORREA DE FREITAS, MARCELA CRISTINA; PICANCO-CASTRO, VIRGINIA; SOARES NETO, MARIO DE ABREU; SWIECH, KAMILLA; COVAS, DIMAS TADEU; DE SOUSA RUSSO, ELISA MARIA. Human cell lines: A promising alternative for recombinant FIX production. Protein Expression and Purification, v. 121, p. 149-156, MAY 2016. Web of Science Citations: 2.
FERRAZ DO AMARAL, ROBSON LUIS; BOMFIM, ALINE DE SOUSA; DE ABREU-NETO, MARIO SOARES; PICANCO-CASTRO, VIRGINIA; DE SOUSA RUSSO, ELISA MARIA; COVAS, DIMAS TADEU; SWIECH, KAMILLA. Approaches for recombinant human factor IX production in serum-free suspension cultures. Biotechnology Letters, v. 38, n. 3, p. 385-394, MAR 2016. Web of Science Citations: 4.
CARON, ANGELO LUIS; PICANCO-CASTRO, VIRGINIA; ANSORGE, SVEN; COVAS, DIMAS TADEU; KAMEN, AMINE; SWIECH, KAMILLA. Production of Lentiviral Vectors Encoding Recombinant Factor VIII Expression in Serum-Free Suspension Cultures. Brazilian Archives of Biology and Technology, v. 58, n. 6, p. 923-928, NOV-DEC 2015. Web of Science Citations: 1.
BIAGGIO, RAFAEL TAGE; ABREU-NETO, MARIO SOARES; COVAS, DIMAS TADEU; SWIECH, KAMILLA. Serum-free suspension culturing of human cells: adaptation, growth, and cryopreservation. Bioprocess and Biosystems Engineering, v. 38, n. 8, p. 1495-1507, AUG 2015. Web of Science Citations: 6.
PICANCO-CASTRO, VIRGINIA; BIAGGIO, RAFAEL TAGE; COVA, DIMAS TADEU; SWIECH, KAMILLA. Production of Recombinant Therapeutic Proteins in Human Cells: Current Achievements and Future Perspectives. PROTEIN AND PEPTIDE LETTERS, v. 20, n. 12, SI, p. 1373-1381, DEC 2013. Web of Science Citations: 13.

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