Friday, March 23, 2007

A potentially radical new approach to genetic engineering and production of precious proteins




We are currently living in the era of genetic engineering, harnessing bacteria and yeasts for the purpose of producing recombinant proteins.

However, one major setback would be the folding of the recombinant proteins especially within the milieu of the bacterial cells. For example, the Georgiou lab at the University of Texas seeks to understand the physiological basis behind the formation of the correct disulphide bonds.

I doodled a possibly radical genetic engineering method of producing a desired protein in large quantities.

1) The first step involves genetic engineering of a virus that is capable of infecting mammalian cells. The lytic phase promoter elements should be present and should activate the transcription of the gene encoding the protein(s) of interest. The virus should be able to shuttle between lytic and lysogenic phase.

2) Infect an immortal mammalian cell-line, preferably a tumor cell-line that is capable of quick division. The infected tumor cells are allowed to multiply when the virus is in its lysogenic phase, whereby there is potential for transmission of viral genetic material to the daughter cells of the tumor cells.

3) When tumor cells with the embedded viral genome reaches exponential growth, expose cells to stimuli that can induce lytic phase, e.g. stress. There will be production of large amounts of the desired protein during the lytic phase.


I would believe this radical approach is immune from the problem of protein folding since the folding takes place inside the mammalian cell-line. It is able to harness the ability of the virus to hijack the cellular machinery and produce large amounts of its proteins, with the genetically engineered virus producing large amounts of precious proteins instead. It also takes advantages of the ability of mammalian tumor cells to divide quickly, thereby transmitting the viral genome to the daughter cells during the lysogenic phase.

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