重组人Beta-干扰素的CHO表达和无血清细胞培养的研究
摘要
Interferon (IFN) is a cytokine family which was discovered to be secreted by cells in response to viral infections. Interferon can be divided into two distinct types: type I and type. IFN-beta is a member of type I IFNs. It has 166 amino acids with a molecular weight of about 22,000 daltons. When binds to its receptors, IFN-beta induces several signal cascades, including the Jak-Stat pathway, the IRS pathway, the CrkL pathway and the p38 Map kinase pathway. Through these pathways, IFN-beta can mediate diverse biological activities such as antiviral infection, proliferation inhibition, apoptosis induction and immunomodulation.
Multiple sclerosis (MS) is a chronic disease of the central nerve system, which is characterized by the progressive destruction of the myelin of nerves of the brain and spinal cord. So far there is no cure for MS. With the wide use of IFN-beta in the treatment of MS in the Western countries, however, the management of the disease has been improved significantly, though the mechanism of action of IFN-beta on MS remains to be investigated. At present, IFN-beta has become the benchmark for the treatment of MS. Three IFN-beta products (Betaseron(?), Avonex(?) and Rebif(?)) have been approved for the treatment of MS in the US and EU, and the global sale of these products has reached 4 billion US dollars in 2005.
The IFN-beta on the market can be divided into two types: IFN-beta-1b and IFN-beta-1a. IFN-beta-1b is bacteria-derived and non-glycosylated, whereas IFN-1a is CHO-cell-produced and glycosylated. Because mammalian cells have a posttranslational modification system, IFN-beta obtained from CHO cell culture was similar to the native counterpart and showed better activity in antiviral, antiproliferative and immunomodulatory assays when compared with the non-glycosylated IFN-beta. In addition, the incidence of neutralizing antibodies to IFN-beta in patients receiving CHO-cell-derived IFN-beta was lower than in patients receiving bacteria-derived IFN-Beta
It is hypothesized that IFN-beta has the activity of inhibiting cell proliferation and inducing apoptosis, the expression of IFN-beta in mammalian cells would potentially
引文
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