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Current Medicinal Chemistry

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Review Article

Gene Therapy as the New Frontier for Sickle Cell Disease

Author(s): Himanshu Garg, Kristina J. Tatiossian, Karsten Peppel, Gregory J. Kato and Eva Herzog*

Volume 29, Issue 3, 2022

Published on: 23 August, 2021

Page: [453 - 466] Pages: 14

DOI: 10.2174/0929867328666210527092456

Price: $65

Abstract

Sickle Cell Disease (SCD) is one of the most common monogenic disorders caused by a point mutation in the β-globin gene. This mutation results in polymerization of hemoglobin (Hb) under reduced oxygenation conditions, causing rigid sickle-shaped RBCs and hemolytic anemia. This clearly defined fundamental molecular mechanism makes SCD a prototypical target for precision therapy. Both the mutant β-globin protein and its downstream pathophysiology are pharmacological targets of intensive research. SCD also is a disease well-suited for biological interventions like gene therapy. Recent advances in hematopoietic stem cell (HSC) transplantation and gene therapy platforms, like Lentiviral vectors and gene editing strategies, expand the potentially curative options for patients with SCD. This review discusses the recent advances in precision therapy for SCD and the preclinical and clinical advances in autologous HSC gene therapy for SCD.

Keywords: Sickle cell disease, gene therapy, gene editing, hematopoietic stem cells, stem cell transplant, precision therapy.

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