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Abstract

Plasmids which are in themselves unstably inherited or which have become unstable due to the insertion of a DNA fragment comprising one or more genes not naturally related to the plasmid are stablized by means of a partitioning function exerted by a par region, especially a plasmid R1 par region, inserted into the plasmid on a DNA fragment which may be the length of the wild-type R1 EcoR1-. A fragment, but which is preferably shorter than this fragment, and which may comprise the R1 par region A, the R1 par region B or both these R1 par regions. The stabilization obtained for several different types of plasmid, especially by employing both R1 par regions, approaches the stability level of wild-type plasmids, i.e. they typically have a frequency of loss of less than 5.times.10.sup.31 6 per cell per generation. Such stabilized plasmids are useful in large-scale production of gene products as no particular bacterial strains or mutants are needed to secure plasmid maintenance, and as is not necessary to employ a specific composition of the nutrient medium in which the host cells are grown in order to prevent loss of the plasmid from the bacterial population.

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