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

ABSTRACT:

Background & aims

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 I (HT-I). We compared the standard of care-nitisinone, a small molecule inhibitor of hydroxyphenylpyruvate dioxygenase (HPD)-with the deletion of the Hpd gene by CRISPR gene therapy. Both treatments block flux through tyrosine catabolism and thereby prevent the accumulation of toxic catabolites in HT-I.

Methods

We assessed the efficacy and safety of CRISPR gene editing in fumarylacetoacetate hydrolase-deficient (Fah-/-) mice, the mouse model

SUBMITTER: Chen T 

PROVIDER: S-EPMC11985117 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature