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Miliotou AN, Papagiannopoulou D, Vlachaki E, et al. PTD-mediated delivery of α-globin chain into Κ-562 erythroleukemia cells and α-thalassemic (HBH) patients' RBCs ex vivo in the frame of Protein Replacement Therapy. J Biol Res (Thessalon). 2021;28(1):16doi: 10.1186/s40709-021-00148-3.
Miliotou, A. N., Papagiannopoulou, D., Vlachaki, E., Samiotaki, M., Laspa, D., Theodoridou, S., Tsiftsoglou, A. S., & Papadopoulou, L. C. (2021). PTD-mediated delivery of α-globin chain into Κ-562 erythroleukemia cells and α-thalassemic (HBH) patients' RBCs ex vivo in the frame of Protein Replacement Therapy. Journal of biological research (Thessalonike, Greece), 28(1), 16. https://doi.org/10.1186/s40709-021-00148-3
Miliotou, Androulla N, et al. "PTD-mediated delivery of α-globin chain into Κ-562 erythroleukemia cells and α-thalassemic (HBH) patients' RBCs ex vivo in the frame of Protein Replacement Therapy." Journal of biological research (Thessalonike, Greece) vol. 28,1 (2021): 16. doi: https://doi.org/10.1186/s40709-021-00148-3
Miliotou AN, Papagiannopoulou D, Vlachaki E, Samiotaki M, Laspa D, Theodoridou S, Tsiftsoglou AS, Papadopoulou LC. PTD-mediated delivery of α-globin chain into Κ-562 erythroleukemia cells and α-thalassemic (HBH) patients' RBCs ex vivo in the frame of Protein Replacement Therapy. J Biol Res (Thessalon). 2021 Jul 20;28(1):16. doi: 10.1186/s40709-021-00148-3. PMID: 34284828; PMCID: PMC8290593.
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J Biol Res (Thessalon). 2021 Jul 20;28(1):16. doi: 10.1186/s40709-021-00148-3.

PTD-mediated delivery of α-globin chain into Κ-562 erythroleukemia cells and α-thalassemic (HBH) patients' RBCs ex vivo in the frame of Protein Replacement Therapy.

Journal of biological research (Thessalonike, Greece)

Androulla N Miliotou, Dionysia Papagiannopoulou, Efthymia Vlachaki, Martina Samiotaki, Dimitra Laspa, Stamatia Theodoridou, Asterios S Tsiftsoglou, Lefkothea C Papadopoulou

Affiliations

  1. Laboratory of Pharmacology, Department of Pharmacognosy - Pharmacology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124, Thessaloniki, Macedonia, Greece.
  2. Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124, Thessaloniki, Macedonia, Greece.
  3. Adult Thalassemia Unit, Hippokrateion General Hospital, 54642, Thessaloniki, Macedonia, Greece.
  4. Institute for Bioinnovation, Biomedical Sciences Research Centre "Alexander Fleming", 16672, Vari, Greece.
  5. Laboratory of Pharmacology, Department of Pharmacognosy - Pharmacology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124, Thessaloniki, Macedonia, Greece. [email protected].

PMID: 34284828 PMCID: PMC8290593 DOI: 10.1186/s40709-021-00148-3

Abstract

BACKGROUND: α-Thalassemia, a congenital hemoglobinopathy, is characterized by deficiency and/or reduced levels of α-globin chains in serious forms of α-thalassemia (HbH disease/Hb Bart's). This research work deals with a Protein Replacement Therapy approach in order to manage α-thalassemia manifestations, caused by the excess of β-globin chain into HbH RBCs. The main goal was to produce the recombinant human α-globin chain in fusion with TAT, a Protein Transduction Domain, to ex vivo deliver it into HbH patients RBCs, to replace the endogenous missing α-globin chain.

RESULTS: Cloning of the α-globin coding sequence, fused to the nucleotide sequence of TAT peptide was conducted and the human recombinant fusion proteins, 10xHis-Xa

CONCLUSIONS: Our data confirm the successful ex vivo transduction of recombinant α-globin chains in HbH RBCs to replace the missing a-globin chain and reduce the HbH-inclusion bodies, seen in α-thalassemias. These findings broaden the possibility of applying a Protein Replacement Therapy approach to module sever forms of α-thalassemia, using recombinant α-globin chains, through PTD technology.

© 2021. The Author(s).

Keywords: HbH thalassemic patients’ RBCs; Intracellular transduction via PTD; LC − MS/MS analysis; Size exclusion chromatography; TAT-α-globin

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