CRISPR/Cas9 gene therapy increases the risk of tumorigenesis in the mouse model of hereditary tyrosinemia type I

The therapeutic potential of CRISPR gene editing has been demonstrated in various animal models; however, little is known about its long-term consequences. This study seeks to bridge this gap by investigating the lasting consequences of CRISPR gene therapy in an animal model of hereditary tyrosinemia type 1 (HT-1). We compared the standard of care —nitisinone, a small molecule inhibitor of hydroxyphenylpyruvate dioxygenase (HPD) — to the deletion of the Hpd gene by CRISPR gene therapy. Both treatments block flux through the tyrosine catabolism and thereby prevent accumulation of toxic catabolites in HT-1.