Generation of improved human PAH for the treatment of severe PKU by liver-specific gene replacement therapy

摘要

Provided herein are variant PAH polypeptides that are more stable and have greater activity than wild-type human phenylalanine hydroxylase (PAH). Also provided are methods of treating and/or reducing phenylketonuria (PKU) in a subject in need thereof. Also provided herein are expression cassettes, vectors (eg, rAAV vectors), viral particles, pharmaceutical compositions, and kits for expressing variant PAH polypeptides in a subject in need thereof.