Innovations in protein design and evolution herald new horizons for therapeutic development. The T7-ORACLE platform accelerates continuous directed evolution of proteins inside living cells by leveraging an engineered bacteriophage replication system, achieving mutation rates up to 100,000-fold higher than natural rates. This technology enables rapid evolution for antibodies, enzymes, and drug target studies. Related advances include methods to mimic ATP-driven protein modification and the creation of flexible, stimuli-responsive DNA nanostructures.