Ad5.CB-hOTC

Ad5.CB-hOTC is a first-generation recombinant adenoviral vector (serotype 5) designed for gene replacement therapy in patients with ornithine transcarbamylase (OTC) deficiency, an X-linked urea cycle disorder. The vector carries a human cDNA for the OTC enzyme under the control of a chicken beta-actin (CB) promoter and a cytomegalovirus (CMV) enhancer. It was developed by the Gene Therapy Program at the University of Pennsylvania to restore hepatic urea cycle function by delivering functional copies of the OTC gene directly to hepatocytes. The drug is historically significant due to the 1999 Phase 1 clinical trial where the death of 18-year-old participant Jesse Gelsinger, caused by a massive systemic inflammatory response to the high dose of the adenoviral vector, led to the immediate termination of the program and a major shift in the oversight and safety protocols for gene therapy globally.

Other names

recombinant adenovirus human ornithine transcarbamylase geneAdOTCAdenoviral human ornithine transcarbamylase