Sickle Cell Disease: From Genetics to Curative Approaches

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Sickle cell disease (SCD) is a monogenic blood disorder caused by a mutation in the beta-globin gene.
• Abnormal sickle hemoglobin (HbS) polymerization under low-oxygen conditions leads to red blood cell sickling.
• Clinical presentation of SCD exhibits significant variability, ranging from severe complications to a normal lifespan.

Purpose of the Study:

• To review genetic factors and modifier genes influencing SCD severity.
• To explore the latest gene therapy advances for SCD treatment.
• To consider SCD as a complex, multifactorial disorder for treatment development.

Main Methods:

• Review of genetic factors, polymorphisms, and modifier genes impacting globin expression and SCD severity.
• Analysis of lentiviral-vector-based approaches in gene therapy for SCD.
• Evaluation of gene-editing strategies for SCD treatment.

Main Results:

• Genetic modulators play a role in the variable clinical presentation of SCD.
• Gene therapy, including lentiviral vectors and gene editing, shows promise for SCD treatment.
• Understanding SCD as a complex disorder is crucial for effective therapeutic strategies.

Conclusions:

• Genetic modifiers significantly influence the diverse clinical outcomes in sickle cell disease.
• Emerging gene therapies present novel avenues for managing SCD.
• A multifactorial approach is essential for advancing pharmacological and genetic treatments for SCD.