Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin β Subunit to the N-Terminal and C-Terminal Coding Sequence
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 t...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2011-01-01
|
| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2011/275063 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832564112297558016 |
|---|---|
| author | Fuad Fares Avri Havron Eyal Fima |
| author_facet | Fuad Fares Avri Havron Eyal Fima |
| author_sort | Fuad Fares |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2544f8fda7ba4c0ba11c032db51c09ea |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-2544f8fda7ba4c0ba11c032db51c09ea2025-02-03T01:11:47ZengWileyInternational Journal of Cell Biology1687-88761687-88842011-01-01201110.1155/2011/275063275063Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin β Subunit to the N-Terminal and C-Terminal Coding SequenceFuad Fares0Avri Havron1Eyal Fima2Department of Human Biology, Faculty of Natural Sciences, University of Haifa and Department of Molecular Genetics, Carmel Medical Center, Mount Carmel, 31905 Haifa, IsraelModigeneTech, Weizmann Science Park, 74140 Nes-Ziona, IsraelModigeneTech, Weizmann Science Park, 74140 Nes-Ziona, IsraelA 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.http://dx.doi.org/10.1155/2011/275063 |
| spellingShingle | Fuad Fares Avri Havron Eyal Fima Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin β Subunit to the N-Terminal and C-Terminal Coding Sequence International Journal of Cell Biology |
| title | Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin β Subunit to the N-Terminal and C-Terminal Coding Sequence |
| title_full | Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin β Subunit to the N-Terminal and C-Terminal Coding Sequence |
| title_fullStr | Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin β Subunit to the N-Terminal and C-Terminal Coding Sequence |
| title_full_unstemmed | Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin β Subunit to the N-Terminal and C-Terminal Coding Sequence |
| title_short | Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic Gonadotropin β Subunit to the N-Terminal and C-Terminal Coding Sequence |
| title_sort | designing a long acting erythropoietin by fusing three carboxyl terminal peptides of human chorionic gonadotropin β subunit to the n terminal and c terminal coding sequence |
| url | http://dx.doi.org/10.1155/2011/275063 |
| work_keys_str_mv | AT fuadfares designingalongactingerythropoietinbyfusingthreecarboxylterminalpeptidesofhumanchorionicgonadotropinbsubunittothenterminalandcterminalcodingsequence AT avrihavron designingalongactingerythropoietinbyfusingthreecarboxylterminalpeptidesofhumanchorionicgonadotropinbsubunittothenterminalandcterminalcodingsequence AT eyalfima designingalongactingerythropoietinbyfusingthreecarboxylterminalpeptidesofhumanchorionicgonadotropinbsubunittothenterminalandcterminalcodingsequence |