A profusion of new applications for phage technologies has been developed within the last few years, stimulating investigations into the large-scale production of different phages. Applications such as antibiotic replacement, phages as gene therapy vectors, phages as vaccines, diagnostics using filamentous phages and novel optical applications such as the phage laser may need grams to kilogrammes of phage in the future. However, many of the techniques that are used for the growth and purification of bacteriophage at small scale are not transferable to large-scale production facilities of phage in industrial processes. In this chapter, the stages of production that need to be carried out at scale are examined for the efficient large-scale fermentation of the filamentous phage M13 and the Siphoviridae phage lambda (λ). A number of parameters are discussed: the multiplicity of infection (MOI) of phage to host cells, the impact of agitation on the initial infection stages, the co-growth with phage rather than static attachment, the use of engineered host cells expressing nuclease, the optimisation of both the quantity and the physiology of the E. coli inoculum and phage precipitation methods.
Part of the book: Bacteriophages