A transformative platform named T7-ORACLE has been developed by researchers at Scripps Research Institute to accelerate directed protein evolution inside living cells. Leveraging an orthogonal T7 replisome system that selectively replicates target genes, this approach achieves mutation rates approximately 100,000 times higher than natural levels without harming host cells. The platform enables thousands-fold faster generation of functional protein variants, dramatically expediting the development of antibodies, enzymes with novel activities, and studies on resistance mutations relevant to therapeutics.