Particle.news

Download on the App Store

Scripps Researchers Deploy T7-ORACLE to Rapidly Evolve Proteins in E. coli

An engineered T7 replisome targets plasmids to introduce mutations at 100,000× normal rates per cell cycle, enabling the evolution of new enzymes in days.

Overview

  • T7-ORACLE confines error-prone T7 DNA polymerase to plasmid replication so the host genome remains untouched while mutation rates surge by 100,000-fold.
  • By coupling hypermutation and selection with each bacterial division, the platform achieves continuous directed evolution without manual intervention.
  • In under a week, the system produced TEM-1 β-lactamase variants that withstand antibiotic levels 5,000 times higher than the original enzyme.
  • The workflow integrates seamlessly with standard E. coli cultures and lab equipment, removing barriers posed by previous continuous evolution methods.
  • Researchers are now applying T7-ORACLE to engineer therapeutic enzymes, cancer-targeting proteases and polymerases for synthetic nucleic acids.