8^th Euro Biotechnology Congress

Biography

Biography: Fuad Fares

Abstract

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 probl em, 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  (hCG) subunit. The CTP contains 28 amino acids with four O-linked oligosaccharide recognition sites. It was postulated that O-linked oligosaccharides add f lexibility, 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) 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.