Human Interferon Beta-lb Production in Pseudomonas fluorescens Using the Pfenex. Expression Technology Platform

摘要

Interferon beta-lb is a protein in the interferon family used to treat the relapsing-remitting form of multiple sclerosis (MS). Interferon beta-lb is a natural human protein (molecular weight -18,500 Da) that is produced in the body in response to viral infection and has antiviral activity. It has been shown to slow the advance of MS and reduce the frequency of attacks. It is believed that interferon-beta achieves this effect on MS progress via its anti-inflammatory properties. Interferon beta-lb drugs have been approved for over 20 years to treat the symptoms of MS. Interferon beta-1b is produced as a recombinant protein in the bacterium E. coli by fermentation and subsequent purification to the active drug. The E. coli bacteria produce the interferon beta-lb molecule at low yield and as an insoluble and inactive product. As part of the purification process, the molecule must be restored to its active state, a process known as refolding. Refolding a protein molecule is a difficult, inefficient, and costly process. If interferon beta-1 b could be produced by a bacterium at high yield in a fully active form without the necessity of refolding, it would be much less expensive to produce and could be offered to patients at a more affordable price.