In vivo correction of human phenylketonuria variants via base and prime editing

Recorded On: 01/10/2024

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Dominique Brooks will discuss pre-clinical data for two therapeutic leads for the treatment of phenylketonuria.   


Overview of Presentation:

  • The c.1222C>T (R408W) variant in the phenylalanine hydroxylase gene (PAH) is the most frequent variant of phenylketonuria (PKU).  
  • The c.1222C>T variant is amendable to corrective editing by base editing and prime editing.  
  • Using a prime-edited hepatocyte cell line and a humanized PKU mouse model, we demonstrate efficient in vitro and in vivo correction of the c.1222C>T variant with base editing and prime editing.  
  • Whole-liver corrective editing results in complete normalization of blood Phe levels.  
  • Base editing and prime editing are viable therapeutic strategies to treat the c.1222C>T PKU variant. 

Dominique Brooks, BS

Graduate Student

University of Pennsylvania

Dominique Brooks is a third-year Ph.D. student in the Gene Therapy and Vaccines Program at University of Pennsylvania. Her research focuses on the development of gene-editing therapies aimed at addressing metabolic diseases, with a specific focus on phenylketonuria. Dominique earned her Bachelor of Science degree from University of Maryland, Baltimore County and distinguished herself as a Meyerhoff Scholar, Howard Hughes Medical Institute Scholar, MARC (Maximizing Access to Research Careers) Scholar, and Barry Goldwater Scholar. Beyond her academic pursuits, Dominique is an IDEAL (Inclusion, Diversity, Equity, and Learner) Research fellow and outreach co-chair for the E.E. Just Biomedical Society where she is an advocate for the advancement of science and education, particularly for those from underrepresented backgrounds. 

Kiran Musunuru, MD, PhD

Professor of Cardiovascular Medicine and Genetics

Perelman School of Medicine at the University of Pennsylvania

An actively practicing cardiologist and committed teacher, Kiran Musunuru, M.D., Ph.D., M.P.H., M.L., is Professor of Cardiovascular Medicine and Genetics in the Perelman School of Medicine at the University of Pennsylvania. His research focuses on the genetics of cardiovascular and metabolic diseases and seeks to identify genetic factors that protect against disease and use them to develop gene-editing therapies. He recently served as Editor-in-Chief of the scientific journal Circulation: Genomic and Precision Medicine. He is author of The CRISPR Generation: The Story of the World's First Gene-Edited Babies and Genome Editing: A Practical Guide to Research and Clinical Applications. He is co-founder and Senior Scientific Advisor of Verve Therapeutics. 

Jessica Chong, PhD (Moderator)

Deputy Editor

HGG Advances


January Journal Club
01/10/2024 at 12:00 PM (EST)  |  Recorded On: 01/10/2024  |  30 minutes
01/10/2024 at 12:00 PM (EST)  |  Recorded On: 01/10/2024  |  30 minutes January Journal Club 2024