A simple and efficient method for the production of human glycosylated glial cell line-derived neurotrophic factor using a Semliki Forest virus expression system

Human glial cell line-derived neurotrophic factor (hGDNF) is a very promising protein for the treatment of Parkinson's disease and other neurodegenerative disorders. The present work describes a quick and simple method to obtain a high amount of purified hGDNF using a mammalian cell-derived sys...

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Detalles Bibliográficos
Autores: Ansorena-Artieda, E. (Eduardo)|||/items/eee6c2d6-f73a-48d3-a5f8-fe090b677c82, Casales, E. (Erkuden)|||/items/2dbe292b-1de8-4e85-a972-8dfa49b6ab00, Aranda, A. (Alejandro)|||/items/32f228f2-4e7d-4eb7-a7d6-46bcfed625bb, Tamayo, E. (Esther)|||/items/10d4cc56-0128-4842-a5fc-2585a32f1e9f, Garbayo, E. (Elisa)|||/items/c0fa35e4-82c5-44f7-b300-740027106dba, Smerdou-Picazo, C. (Cristian)|||/items/48fd1bd4-6483-45c9-9951-8a1b04873227, Blanco-Prieto, M.J. (María José)|||/items/93e177db-635f-456f-b672-b79ef8befc40, Aymerich-Soler, M.S. (María Soledad)|||/items/f65ae32b-d1a8-4fa4-ba9f-b8b10241f470
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/23071
Acceso en línea:https://hdl.handle.net/10171/23071
Access Level:acceso abierto
Palabra clave:GDNF
SFV expression system
Protein expression
Protein purification
BHK cells
Glycosylated recombinant protein
Descripción
Sumario:Human glial cell line-derived neurotrophic factor (hGDNF) is a very promising protein for the treatment of Parkinson's disease and other neurodegenerative disorders. The present work describes a quick and simple method to obtain a high amount of purified hGDNF using a mammalian cell-derived system. The method is based on the high expression level provided by a Semliki Forest virus vector and its ability to induce a strong shut-off of host-cell protein synthesis in mammalian cells. As a result, hGDNF is the only protein present in the supernatant and can be efficiently purified by a single chromatographic step. Using this system it was possible to eliminate other secreted proteins from the culture medium, like insulin-like growth factor-5, which are hard to remove using other hGDNF production methods. Purified hGDNF presents a complex glycosylation pattern typical of mammalian expression systems and is biologically active. This protocol could be extended to other secreted proteins and could be easily scaled up for industrial purposes.