REVIEW article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1630994
This article is part of the Research TopicStrategic Drug Development for Rare and Underexplored DiseasesView all articles
Sickle cell disease: Understanding pathophysiology, clinical features and advances in gene therapy approaches
Provisionally accepted
Muhammad Taher1*
Aisyah Sofea Aminondin1Nur Asyilah Nasir1Noor Afiqah Jasmadi1Nur Irdeena Nizam1Ilhan Syahmi Bin Shahrul1
Deny Susanti1
Junaidi Khotib2*
Muhammad Salahuddin Haris3*- 1International Islamic University Malaysia, Selayang, Malaysia
- 2Universitas Airlangga, Surabaya, Indonesia
- 3Royal College of Medicine Perak, Perak, Malaysia
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Sickle cell disease (SCD) is an inherited blood disorder marked by the production of abnormal hemoglobin, leading to the distortion-or sickling-of red blood cells. The SCD arises from a single-point mutation that substitutes glutamic acid with valine at the sixth codon of the βglobin chain in hemoglobin. This substitution promotes deoxyhemoglobin aggregation, elevating red blood cell stiffness, and triggering vaso-occlusive and hemolytic repercussions.To explore therapeutic advances in tackling this disease, this review analyzed articles published from January 2015 to January 2025 using the three databases using relevant keywords focusing on SCD and advancement in therapy. It was found that allogeneic hematopoietic stem cell (HSC) transplantation can alleviate symptoms but is limited by a shortage of well-matched donors and immunological challenges. In contrast, autologous gene-modified HSC 1 transplantation via gene therapy offers comparable therapeutic benefits without associated immunological complications. Clinical trials utilizing lentiviral vector-mediated gene insertion have demonstrated promising therapeutic outcomes by preventing hemoglobin aggregation.Emerging gene editing approaches such as CRISPR/Cas9 are expanding treatment options, marking the transition of SCD gene therapy from theoretical concept to clinical application.
Keywords: Anemia, Gene Therapy, gene editing, CRISPR, Hemoglobinopathies, Hematopoietic Stem Cell Transplantation
Received: 19 May 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 Taher, Aminondin, Nasir, Jasmadi, Nizam, Bin Shahrul, Susanti, Khotib and Salahuddin Haris. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Muhammad Taher, International Islamic University Malaysia, Selayang, Malaysia
Junaidi Khotib, Universitas Airlangga, Surabaya, Indonesia
Muhammad Salahuddin Haris, Royal College of Medicine Perak, Perak, Malaysia
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