PMID- 34658870
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211022
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - The Future of Gene Therapy for Transfusion-Dependent Beta-Thalassemia: The Power 
      of the Lentiviral Vector for Genetically Modified Hematopoietic Stem Cells.
PG  - 730873
LID - 10.3389/fphar.2021.730873 [doi]
LID - 730873
AB  - beta-thalassemia, a disease that results from defects in beta-globin synthesis, leads 
      to an imbalance of beta- and alpha-globin chains and an excess of alpha chains. Defective 
      erythroid maturation, ineffective erythropoiesis, and shortened red blood cell 
      survival are commonly observed in most beta-thalassemia patients. In severe cases, 
      blood transfusion is considered as a mainstay therapy; however, regular blood 
      transfusions result in chronic iron overload with life-threatening complications, 
      e.g., endocrine dysfunction, cardiomyopathy, liver disease, and ultimately 
      premature death. Therefore, transplantation of healthy hematopoietic stem cells 
      (HSCs) is considered an alternative treatment. Patients with a compatible human 
      leukocyte antigen (HLA) matched donor can be cured by allogeneic HSC 
      transplantation. However, some recipients faced a high risk of 
      morbidity/mortality due to graft versus host disease or graft failure, while a 
      majority of patients do not have such HLA match-related donors. Currently, the 
      infusion of autologous HSCs modified with a lentiviral vector expressing the 
      beta-globin gene into the erythroid progenitors of the patient is a promising 
      approach to completely cure beta-thalassemia. Here, we discuss a history of 
      beta-thalassemia treatments and limitations, in particular the development of 
      beta-globin lentiviral vectors, with emphasis on clinical applications and future 
      perspectives in a new era of medicine.
CI  - Copyright (c) 2021 Rattananon, Anurathapan, Bhukhai and Hongeng.
FAU - Rattananon, Parin
AU  - Rattananon P
AD  - Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol 
      University, Ratchathewi, Thailand.
FAU - Anurathapan, Usanarat
AU  - Anurathapan U
AD  - Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol 
      University, Ratchathewi, Thailand.
FAU - Bhukhai, Kanit
AU  - Bhukhai K
AD  - Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, 
      Thailand.
FAU - Hongeng, Suradej
AU  - Hongeng S
AD  - Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol 
      University, Ratchathewi, Thailand.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20211001
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8517149
OTO - NOTNLM
OT  - allogeneic HSC transplantation
OT  - gene therapy
OT  - hematopoietic stem cells (HSCs)
OT  - lentiviral vector
OT  - transfusion-dependent
OT  - beta-thalassemia
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/10/19 06:00
MHDA- 2021/10/19 06:01
PMCR- 2021/10/01
CRDT- 2021/10/18 08:53
PHST- 2021/06/25 00:00 [received]
PHST- 2021/09/09 00:00 [accepted]
PHST- 2021/10/18 08:53 [entrez]
PHST- 2021/10/19 06:00 [pubmed]
PHST- 2021/10/19 06:01 [medline]
PHST- 2021/10/01 00:00 [pmc-release]
AID - 730873 [pii]
AID - 10.3389/fphar.2021.730873 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Oct 1;12:730873. doi: 10.3389/fphar.2021.730873. 
      eCollection 2021.