This is particularly true of membrane proteins. Even if the protein is expressed poorly from the cloned DNA, the presence of many hundreds of copies of the gene on the plasmid may raise the level of protein to toxic levels. In these cases, using a plasmid with a lower copy number may reduce the gene dosage below a level at which toxicity occurs. For example, pBR322 is based on the original ColE1 replicon and thus has a copy number of 15-20 (11). The pACYC series of plasmids are based on the p15A replicon, which has a copy number of 18-22 (12). Low-copy-number plasmids include pSC101 (copy number around 5) (13), whereas BACs are maintained at one copy per cell (5).