Ornithine transcarbamylase (OTC)

Ornithine transcarbamylase (OTC) is a nuclear-encoded mitochondrial enzyme that plays a pivotal role in the urea cycle, primarily within hepatocytes. It catalyzes the synthesis of citrulline from carbamoyl phosphate and L-ornithine, a critical step in the detoxification of ammonia into urea for renal excretion (UniProt P00480). Deficiency in this enzyme, caused by mutations in the X-linked OTC gene, leads to Ornithine Transcarbamylase Deficiency (OTCD), resulting in toxic accumulations of ammonia that cause neurological damage, coma, or death (NCBI Gene ID: 5009). Modern therapeutic approaches, such as AAV8-mediated gene delivery, utilize adeno-associated virus vectors to deliver a codon-optimized human OTC gene (hOTCco) directly to the liver. This strategy aims to restore stable enzyme expression and metabolic flux, thereby reducing the reliance on ammonia-scavenging drugs and protein-restricted diets (PubMed: 31553918, ClinicalTrials.gov: NCT02991144).

Other names

Ornithine carbamoyltransferaseOCTOTCase

Gene replacement therapy designed to deliver a functional, codon-optimized human OTC gene to hepatocytes to restore endogenous enzyme activity and normalize the urea cycle.