# Emerging Therapies for Sickle Cell Disease: From Symptom Management to Curative Gene Therapy

## TL;DR

This paper reviews new gene therapies for sickle cell disease that could offer cures instead of just managing symptoms.

## Contribution

The paper evaluates the promise and limitations of emerging gene therapies for sickle cell disease.

## Key findings

- Gene therapies like lentiviral vector-mediated gene addition and CRISPR/Cas9 show curative potential for sickle cell disease.
- Clinical trials report reduced vaso-occlusive crises and transfusion independence with these therapies.
- High costs and limited access remain barriers to widespread use of gene therapies in high-burden regions.

## Abstract

Sickle cell disease (SCD) is a hereditary hemoglobinopathy caused by a point mutation in the β-globin gene, leading to the production of hemoglobin S and resulting in chronic hemolytic anemia, vaso-occlusion, and progressive organ damage. Affecting millions globally, with the highest prevalence in sub-Saharan Africa and other low-resource settings, SCD remains a major public health challenge. Current therapies, including hydroxyurea, L-glutamine, crizanlizumab, and transfusions, primarily offer symptomatic relief but do not correct the underlying genetic defect. Hematopoietic stem cell transplantation remains the only established cure but is limited by donor availability and associated risks. Recent advances in gene therapy have transformed the therapeutic landscape of SCD, offering curative potential through techniques such as lentiviral vector-mediated gene addition and CRISPR/Cas9 gene editing. These approaches aim to restore normal hemoglobin production or reactivate fetal hemoglobin expression. While clinical trial outcomes are encouraging, with reduced vaso-occlusive crises and transfusion independence, major challenges remain, including high costs, need for myeloablative conditioning, and limited access in high-burden regions. This review explores the evolution of SCD treatment, evaluates the promise and limitations of emerging gene therapies, and highlights the urgent need for equitable access to these transformative technologies.