The invention relates to modifying plasmid origins of replication to create hybrid origins of replication containing nucleotide sequences from more than one plasmid. The invention also relates to a modified origin of replication cassette that is portable or exchangeable due to the creation of multiple cloning sites flanking the origin of replication. Methods and plasmids for use in exchanging origins of replication are disclosed. Such modified or hybrid plasmids provide useful cloning tools that allow for regulation of the level of expression of a desired protein.