Help a biochemist out?

Are you doing mol bio or biochem or anything where you're trying to get a mutation to go into a genome?

We've got this system where we can easily get a plasmid with our copy of the gene with the mutation. However, we have to transform into a system where this mutated copy of the gene needs to get into all of the copies of the gene within the native system (otherwise we'll have 75% mutated protein and 25% wild type protein). We've already got antibiotic resistance as a selector, but cells that transform partially still grow. We've got another type of nutrient related selection. But we keep on getting not the full mutation back when we sequence it because our screening system isn't selecting for just the cells where the mutation is in every copy of the gene.

Anyone out there got some awesome ideas for screening? I'm looking and racking my brain, but this is not my field of expertise.