OrthoRep-Driven Antibody Evolution

Please register via: https://us06web.zoom.us/webinar/register/WN_c3IAFMwOQH2U8MbmUsp97w#/registration

OrthoRep-Driven Antibody Evolution

Abstract: 

Antibody engineering relies heavily on directed evolution to optimize target affinity and specificity. However, traditional in vitro selection techniques—such as phage display or iterative mutagenesis libraries—remain bottlenecked by manual interventions, limited library sampling, and discrete round-based protocols. To overcome these constraints, continuous in vivo targeted hypermutation offers a transformative alternative by enabling rapid, automated, and continuous sequence space exploration on laboratory timescales. 

In this webinar, Dr. Chang Liu will present recent developments from his group on leveraging Orthogonal DNA Replication (OrthoRep)- a breakthrough continuous evolution platform that dramatically accelerates mutation rates in vivo without compromising host genome integrity. Attendees will gain deep insights into how OrthoRep enables researchers to prospectively track and systematically manipulate complex, multi-step gene evolutionary trajectories. 

Dr. Liu will highlight how his team scales affinity maturation of therapeutic antibodies and bridges continuous directed evolution with modern machine learning. Specifically, the presentation will showcase strategies for prioritizing sequence space exploration to generate rich, unbiased evolutionary datasets essential for training and refining predictive computational models. Join us to explore how OrthoRep is reshaping the convergence of synthetic biology, antibody discovery, and data-driven protein design.

Speaker Bio:

Dr. Chang Liu graduated summa cum laude and Phi Beta Kappa from Harvard in 2005 with a degree in chemistry, carried out his PhD at the Scripps Research Institute as a Hertz Fellow, and did his postdoc at UC Berkeley as a Miller Fellow, and started his independent group in 2013. 

Dr. Liu’s group engineers specialized genetic systems that continuously and rapidly mutate user-selected genes in vivo. These systems are used to accelerate and scale directed evolution, generate strategic evolutionary datasets for ML, and record developmental biological processes. 

Dr. Liu’s group is best known for their development of orthogonal DNA replication (OrthoRep), a genetic architecture that achieves durable continuous hypermutation and evolution of target genes in vivo. OrthoRep has been applied to a range of protein engineering problems including the generation of therapeutic antibodies and commercial enzymes. It has also been used to probe how evolution searches sequence-function landscapes. 

For his group’s outstanding work, Dr. Liu has been recognized by the NIH Director’s Transformative Research Award, The Moore Inventor Fellowship, The Robert W. Vaughan Lectureship at Caltech, the NIH New Innovator Award, the Beckman Young Investigator Award, the ACS Synthetic Biology Young Innovator Award, and selection as a Sloan Fellow, a Kavli Fellow, a Blavatnik National Awards for Young Scientists Finalist, and a member of the AIMBE College of Fellows.