Sickle cell disease: understanding pathophysiology, clinical features and advances in gene therapy approaches
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 β-globin chain in hemog...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1630994/full |
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| author | Muhammad Taher Sofea ‘Aisyah Aminondin Nur Asyilah Nasir Noor Afiqah Jasmadi Nur Irdeena Nabella Nizam Ilhan Syahmi Shahrul Deny Susanti Junaidi Khotib Md Faiyazuddin Riyanto Teguh Widodo Muhammad Salahuddin Haris |
| author_facet | Muhammad Taher Sofea ‘Aisyah Aminondin Nur Asyilah Nasir Noor Afiqah Jasmadi Nur Irdeena Nabella Nizam Ilhan Syahmi Shahrul Deny Susanti Junaidi Khotib Md Faiyazuddin Riyanto Teguh Widodo Muhammad Salahuddin Haris |
| author_sort | Muhammad Taher |
| collection | DOAJ |
| description | 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 β-globin 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 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. |
| format | Article |
| id | doaj-art-af9a309622cd4f9b9256205f2da19c2f |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-af9a309622cd4f9b9256205f2da19c2f2025-08-22T08:51:34ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-08-011610.3389/fphar.2025.16309941630994Sickle cell disease: understanding pathophysiology, clinical features and advances in gene therapy approachesMuhammad Taher0Sofea ‘Aisyah Aminondin1Nur Asyilah Nasir2Noor Afiqah Jasmadi3Nur Irdeena Nabella Nizam4Ilhan Syahmi Shahrul5Deny Susanti6Junaidi Khotib7Md Faiyazuddin8Riyanto Teguh Widodo9Muhammad Salahuddin Haris10Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, MalaysiaFaculty of Pharmacy, International Islamic University Malaysia, Kuantan, MalaysiaFaculty of Pharmacy, International Islamic University Malaysia, Kuantan, MalaysiaFaculty of Pharmacy, International Islamic University Malaysia, Kuantan, MalaysiaFaculty of Pharmacy, International Islamic University Malaysia, Kuantan, MalaysiaFaculty of Pharmacy, International Islamic University Malaysia, Kuantan, MalaysiaDepartment of Chemistry, Faculty of Science, International Islamic University Malaysia, Kuantan, MalaysiaDepartment of Pharmacy Practice, Faculty of Pharmacy, Airlangga University, Surabaya, IndonesiaCentre for Global Health Research, Saveetha Institute of Medical and Technical Sciences, Chennai, IndiaDepartment of Pharmaceutical Technology, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, MalaysiaDepartment of Pharmacy, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, MalaysiaSickle 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 β-globin 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 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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1630994/fullanemiagene therapygene editingCRISPRhemoglobinopathieshematopoietic stem cell transplantation |
| spellingShingle | Muhammad Taher Sofea ‘Aisyah Aminondin Nur Asyilah Nasir Noor Afiqah Jasmadi Nur Irdeena Nabella Nizam Ilhan Syahmi Shahrul Deny Susanti Junaidi Khotib Md Faiyazuddin Riyanto Teguh Widodo Muhammad Salahuddin Haris Sickle cell disease: understanding pathophysiology, clinical features and advances in gene therapy approaches Frontiers in Pharmacology anemia gene therapy gene editing CRISPR hemoglobinopathies hematopoietic stem cell transplantation |
| title | Sickle cell disease: understanding pathophysiology, clinical features and advances in gene therapy approaches |
| title_full | Sickle cell disease: understanding pathophysiology, clinical features and advances in gene therapy approaches |
| title_fullStr | Sickle cell disease: understanding pathophysiology, clinical features and advances in gene therapy approaches |
| title_full_unstemmed | Sickle cell disease: understanding pathophysiology, clinical features and advances in gene therapy approaches |
| title_short | Sickle cell disease: understanding pathophysiology, clinical features and advances in gene therapy approaches |
| title_sort | sickle cell disease understanding pathophysiology clinical features and advances in gene therapy approaches |
| topic | anemia gene therapy gene editing CRISPR hemoglobinopathies hematopoietic stem cell transplantation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1630994/full |
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