Site-Specific Albumination of Therapeutic Proteins for the Prolonged Serum Half-Life In Vivo
- Conference: International Conference Biomolecular Engineering ICBE
- Year: 2018
- Proceeding: ICBE Asia 2018: International Conference on Biomolecular Engineering
- Group: General Submissions
- Time: Tuesday, January 9, 2018 - 9:05am-9:30am
Gout is a common inflammatory arthritis. The number of people affected by gout reached three millions in US in 1999. Gout is caused by abnormally high concentration of insoluble uric acid in the blood. One way to treat gout is conversion of uric acid into a soluble metabolite by urate oxidase enzyme. PEGylated urate oxidase was approved by FDA for gout treatment. However, immune concerns associated PEG molecules drove search for alternative way to prolong the serum half-life. We used site-specific incorporation of a clickable non-natural amino acid and click chemistry to site-specifically conjugate a human serum albumin to urate oxidase (Uox-HSA). Uox-HSA exhibited the significantly longer serum half-life in animal studies without compromising the therapeutic activities upon HSA conjugation. Using similar techniques, fatty acid, a natural HSA ligand, was site-specifically conjugated to Uox for the enhanced HSA binding affinity without a substantial loss in the therapeutic activities. Furthermore, injectable hydrogels conjugated to HSA allowed the sustained release of fatty acid-conjugated Uox in vivo.