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

Description

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.