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A simple model is developed that permits the determination of cellular extrachromosomal DNA content for a large number of host-plasmid systems. The model incorporates host, vector, and environmental influences on plasmid replication through the use of empirical expressions. The model successfully predicts the plasmid content of many host-vector systems in a balanced growth situation, both in continuous and batch cultures. Techniques for determining model parameters are also presented. The model parameters, which characterize the effect of plasmid on its own synthesis, are given physical interpretation through the development of a structured model for a particular class of plasmids and subsequent comparison of the predictions of the two models. The simplicity of the model expressions should, in the absence of: (1) discriminatory criteria such as plasmid concentration under transient growth conditions or (2) detailed knowledge on molecular mechanisms of plasmid replication, prove useful in the study of host-vector systems for genetic engineering applications.

Cellular plasmid content determines the yield of closed-gene product, affects plasmid replication, and influences the behavior of the culture by dictating the extent of metabolic burden on the host cell and plasmid segregation at cell division. Hence, it is a variable of primary importance in the study of recombinant cell cultures. In this article, equations are developed to enable the conversion of experimental determinations of cellular plasmid content into theoretically important units. The importance of different units in characterizing plasmid effect on cell response is highlighted. Also, equations that relate cellular plasmid content to cloned-gene expression are developed and successfully tested on several sets of data from literature.

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