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International Journal of Cell Biology
Volume 2011, Article ID 275063, 7 pages
http://dx.doi.org/10.1155/2011/275063
Research Article

Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin Subunit to the N-Terminal and C-Terminal Coding Sequence

1Department of Human Biology, Faculty of Natural Sciences, University of Haifa and Department of Molecular Genetics, Carmel Medical Center, Mount Carmel, 31905 Haifa, Israel
2ModigeneTech, Weizmann Science Park, 74140 Nes-Ziona, Israel
3PROLOR Biotech, Weizmann Science Park, 74140 Nes-Ziona, Israel

Received 26 February 2011; Accepted 26 June 2011

Academic Editor: Johannes Vogel

Copyright © 2011 Fuad Fares et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A new analog of EPO was designed by fusing one and two CTPs to the N-terminal and C-terminal ends of EPO (EPO-(CTP)3), respectively. This analog was expressed and secreted efficiently in CHO cells. The in vitro test shows that the activity of EPO-(CTP)3 in TFI-1 cell proliferation assay is similar to that of EPO-WT and commercial rHEPO. However, in vivo studies indicated that treatment once a week with EPO-(CTP)3 (15 μg/kg) dramatically increased (~8 folds) haematocrit as it was compared to rHuEPO. Moreover, it was found that EPO-(CTP)3 is more effective than rHuEPO and Aranesp in increasing reticulocyte number in mice blood. The detected circulatory half-lives of rHuEPO, Aranesp, and EPO-(CTP)3 following IV injection of 20 IU were 4.4, 10.8, and 13.1 h, respectively. These data established the rational for using this chimera as a long-acting EPO analog in clinics. The therapeutic efficacy of EPO-CTP analog needs to be established in higher animals and in human clinical trials.