Abstract

β-Thalassemia and sickle cell disease (SCD) are inherited hemoglobinopathies that pose substantial global health challenges. Gene therapy has emerged as a transformative, potentially curative approach by directly targeting the underlying genetic defects responsible for these disorders. This systematic review and meta-analysis critically assessed the clinical efficacy and safety of contemporary gene therapy modalities, including lentiviral-based platforms (e.g., Zynteglo) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9–based approaches (e.g., Casgevy), in patients with β-thalassemia and SCD. A comprehensive literature search spanning January 2013 to March 2025 was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Pooled analyses demonstrated a significant increase in transfusion independence among treated patients (Z = 5.89, p < 0.001), with moderate heterogeneity across studies. Lentiviral gene therapies consistently achieved haemoglobin normalisation and sustained transfusion freedom, whereas early-phase CRISPR trials highlighted favourable safety profiles and high gene-editing precision. Despite these promising outcomes, challenges such as insertional mutagenesis, off-target editing, high therapeutic costs, and limited availability in resource-constrained regions persist. In summary, gene therapy represents a clinically effective and potentially curative intervention for β-thalassemia and SCD. Nonetheless, rigorous long-term safety monitoring and strategies to enhance global accessibility are essential to ensure equitable implementation and sustainable patient outcomes.

Key words: Gene therapy, β-thalassemia, sickle cell disease, CRISPR, lentiviral vectors, gene editing