Journal of Biotechnology & Biomaterials
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One major issue regarding the clinical use of many peptides is their short half-life due to the rapid clearance from the
circulation. To overcome this problem, we succeeded to ligate the signal sequence of O-linked oligosaccharides to the
coding sequence of the hormones. The cassette gene that has been used contains the sequence of the carboxyl-terminal
peptide (CTP) of human chorionic gonadotropin β (hCGβ) subunit. The CTP contains 28 amino acids with four O-linked
oligosaccharide recognition sites. It was postulated that O-linked oligosaccharides add flexibility, hydrophilicity and stability to
the protein. On the other hand, it was suggested that the four O-linked oligosaccharides play an important role in preventing
plasma clearance and thus increasing the half-life of the protein in circulation. Using this strategy, we succeeded to ligate the
CTP to the coding sequence of Follitropin (FSH), Thyrotropin (TSH), Erythropoietin (EPO) and Growth Hormone (GH)
and, thus, to increase the longevity and bioactivity of these proteins in vivo. Interestingly, the new analogs of FSH and GH
were found not immunogenic in human and it is already passed successfully clinical trials phase III and phase II, respectively.
Moreover, FSH long acting was approved by the European Commission (EC) for treatment of fertility. In addition, our results
indicated that long acting GH is not toxic in monkeys and the results from clinical trials phase I and phase II seem to be
promising. Designing long acting peptides will diminish the cost of these drugs and perhaps reduce the number of injections
in the clinical protocols.
Fuad Fares has completed his DSc studies at the Faculty of Medicine, Technion-Israel Institute of Technology and Postdoctoral studies at the Department of Molecular Biology and Pharmacology, School of Medicine, Washington University, St. Louis Missouri. He is the Director of the Department of Molecular Genetics at Carmel Medical Center and Associated Professor at the Department of Human Biology, University of Haifa. He has published more than 75 papers in reputed journals and serving as a Member of the Israel Council for Higher Education. He is the Inventor of designing long-acting recombinant proteins and the initiator of PROLOR Biotech Company.