Abstract: Disclosed herein are methods of performing continuous directed evolution in complex biological systems, including metazoan cells. These methods include the infection of engineered, non-naturally occurring metazoan cells with engineered, non-naturally occurring DNA viruses. The generation of infectious viruses that can infect new cells depends on the evolution of a gene of interest which is driven by an error-prone adenoviral polymerase. Also disclosed herein, are the compositions of engineered, non-naturally occurring metazoan cells and engineered, non-naturally occurring DNA viruses that function as components in the continuous directed evolution methodologies.

Abstract: Disclosed herein are methodologies and kits for dynamic targeted hypermutation that harness the enzymatic activity of a polynucleic acid-binding protein fused to a nucleobase-editing enzyme to specifically target mutations across a region of interest. These methodologies and kits facilitate the rapid creation of diverse DNA libraries in vivo or in vitro.

Abstract: Disclosed herein are methods of performing continuous directed evolution in complex biological systems, including metazoan cells. These methods include the infection of engineered, non-naturally occurring metazoan cells with engineered, non-naturally occurring DNA viruses. The generation of infectious viruses that can infect new cells depends on the evolution of a gene of interest which is driven by an error-prone adenoviral polymerase. Also disclosed herein, are the compositions of engineered, non-naturally occurring metazoan cells and engineered, non-naturally occurring DNA viruses that function as components in the continuous directed evolution methodologies.