Tobacco - a producer of recombinant interferons.

The approved therapeutic interferons, which are chiefly indicated for a treatment of hepatitis C or hairy cell leukaemia (IFN-α), relapsingl remitting sclerosis multiplex (IFN-β) and chronic granulomatous disease (IFN-γ), are commercially produced by recombinant DNA technology, mainly in bacteria Escherichia coli (IFN-α, IFN-β1b, IFN-γ), rarely in a mammalian cell line CHO (IFN-βla). A serum half-life time of some non-glycosylated IFN-α products was extended by a chemical attachment of a branched polyethylene glycol (PEG) to give PEGylated IFN-α. The therapy with recombinant interferons proves expensive and hence much hope is concerned with their production in other platforms assumed to be cheaper, like transgenic plants. Currently, tobacco, botanically species Nicotiana tabacum, its cultivars and some related species, especially N. benthamiana, is one of the most important plant expression systems tested for the production of therapeutical polypeptides and proteins (so-called biopharmaceuticals or biologics), especially vaccines, by using either greenhouse or field cultivated plants or cell suspension culture. IFN-α subtypes were expressed in tobacco nuclear genom e (IFN-α2a and 2b), chloroplast genome (IFN-α2b) and by transient expression (IFN-α2b). The IFα-a2b chimera fusions with O-glycosylated protein with O-a-rabinogalactans expressed in tobacco BY-2 cell culture showed increased half-life time similar to that obtained by PEGylation. The production of IFN-α2b (non-glycosydated) in tobacco glasshouse or field cultivation has been also elaborated. One report concerned expression of IFN-β but with low yield. N-glycosylated IFN-γ could be efficiently expressed in tobacco protoplast infected with recombinant brome mosaic virus (BMV) with the yield of 5-10% of total extracted protein. This type interferon (non-glycosylated), when expressed in chloroplast genome, proved unstable and could be obtained with reasonable yield as a fusion with GUS (β-glucuronidase).