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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  μ g/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.

international journal of cell biology

Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi mathvariant="bold">β</mml:mi></mml:math>Subunit to the<i>N</i>-Terminal and<i>C</i>-Terminal Coding Sequence

Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic GonadotropinβSubunit to theN-Terminal andC-Terminal Coding Sequence