For large genes that need fixing, evolution in a flask generates useful recombinases

For large genes that need fixing, evolution in a flask generates useful recombinases

Take your time with this cartoon, but the key to harnessing evolution of phage proteins with critical roles in "survival of the fittest" is the "mutator plasmid" that greatly accelerates the evolution rate (here mutations are the evolution drivers). Thus, the phages that out compete their competition, contained the best recombinase genes with the desired properties.

"Methods for the targeted integration of genes in mammalian genomes suffer from low programmability, low efficiencies or low specificities. Here we show that phage-assisted continuous evolution enhances prime-editing-assisted site-specific integrase gene editing (PASSIGE), which couples the programmability of prime editing with the ability of recombinases to precisely integrate large DNA cargoes exceeding 10 kilobases."

https://www.nature.com/articles/s41551-024-01227-1

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