• DOI:10.1038/nbt799
• Corpus ID: 7214868

Enhancement of therapeutic protein in vivo activities through glycoengineering

@article{Elliott2003EnhancementOT,
  title={Enhancement of therapeutic protein in vivo activities through glycoengineering},
  author={Steven G. Elliott and Tony Lorenzini and Sheilah J. Asher and Kenneth H. Aoki and David W. Brankow and Lynette Buck and Leigh A. Busse and David Chang and Janis Fuller and James Grant and Natasha Hernday and Martha Hokum and Sylvia Hu and Andrew Knudten and Nancy J Levin and Renee Komorowski and F Bachmann Martin and Rachell Navarro and Timothy D. Osslund and Gary Rogers and Norma Rogers and Geri Trail and Joan C. Egrie},
  journal={Nature Biotechnology},
  year={2003},
  volume={21},
  pages={414-421}
}

• S. Elliott, T. Lorenzini, +20 authors J. Egrie
• Published 1 April 2003
• Biology, Chemistry
• Nature Biotechnology

Delivery of protein therapeutics often requires frequent injections because of low activity or rapid clearance, thereby placing a burden on patients and caregivers. Using glycoengineering, we have increased and prolonged the activity of proteins, thus allowing reduced frequency of administration. Glycosylation analogs with new N-linked glycosylation consensus sequences introduced into the protein were screened for the presence of additional N-linked carbohydrates and retention of in vitro activity. Suitable consensus sequences were combined in one molecule, resulting in glycosylation analogs of rHuEPO, leptin, and Mpl ligand. All three molecules had substantially increased in vivo activity and prolonged duration of action. Because these proteins were of three different classes (rHuEPO is an N-linked glycoprotein, Mpl ligand an O-linked glycoprotein, and leptin contains no carbohydrate), glycoengineering may be generally applicable as a strategy for increasing the in vivo activity and duration of action of proteins. This strategy has been validated clinically for glycoengineered rHuEPO (darbopoetin alfa).