The problem of producing stable DNA plasmids of high copy number may be solved by selecting mutants in which an altered repressor gene leads to high copy number replication. The plasmids are modifed by placing a suitable transcriptional "stop" signal after an inserted heterogenous gene so that the readthrough expression of the heterologous DNA will not continue into the replication primer strand. Deletions resulting from interference with replication primer strand transcription are thereby avoided.
Such plasmids may be used to produce a desired protein by introducing them into a host microorganism and allowing the host to express phenotypically its genotype (including the plasmids).