Process, vectors and engineered cell lines for enhanced...

C - Chemistry – Metallurgy – 12 – N

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Details

C12N 15/85 (2006.01) C07K 14/035 (2006.01) C07K 14/05 (2006.01) C07K 19/00 (2006.01)

Patent

CA 2722835

Processes, vectors and engineered cell lines for large-scale transfection and protein production in mammalian cells, especially Chinese Hamster Ovary (CHO) cells are described in which transfection efficiencies are realized through the use of a single vector system, the use of functional oriP sequences in all plasmids, the use of codon--optimized Epstein-Barr virus nuclear antigen-1 (EBNA1) constructs, the use of a fusion protein between a truncated Epstein-Barr virus nuclear antigen-1c (EBNA1c) protein and a herpes simplex virus protein VP16, the use of a 40 kDa fully deacetylated poly(ethylenimine) as a transfection reagent, the use of co-expression of a fibroblast growth factor (FGF) and/or the use of protein kinase B to potentiate heterologous gene expression enhancement by valproic acid (VPA).

L'invention porte sur des procédés, des vecteurs et des lignées cellulaires manipulées pour la transfection à grande échelle et la production de protéines dans des cellules de mammifère, en particulier des cellules d'ovaire de hamster chinois (CHO), les rendements de transfections étant atteints par l'utilisation d'un système de vecteur unique, l'utilisation de séquences oriP fonctionnelles dans tous les plasmides, l'utilisation d'antigène nucléaire du virus d'Epstein-Barr-1 (EBNA1) recombinant à codons optimisés, l'utilisation d'une protéine de fusion entre une protéine antigène nucléaire du virus d'Epstein-Barr-1c (EBNA1c) tronquée et une protéine VP16 du virus herpès simplex, l'utilisation d'une poly(éthylèneimine) totalement désacétylée de 40 kDa comme réactif de transfection, l'utilisation de la co-expression d'un facteur de croissance des fibroblastes (FGF) et/ou l'utilisation de la protéine kinase B pour potentialiser l'accroissement de l'expression de gènes hétérologues par l'acide valproïque (VPA).

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