GENERATION OF IMPROVED HUMAN PAH FOR TREATMENT OF SEVERE PKU BY LIVER-DIRECTED GENE REPLACEMENT THERAPY

摘要

Provided herein are variant phenylalanine hydroxylase (PAH) polypeptides which are more stable and have greater activity than wild-type human PAH. Also provided are methods to treat phenylketonuria (PKU) and/or to reduce levels of phenylalanine in an individual in need thereof. Further provided herein are expression cassettes, vectors (e.g., rAAV vectors), viral particles, pharmaceutical compositions and kits for expressing the variant PAH polypeptide in an individual in need thereof.