# miRNA-Mediated Regulation of γ-Globin to β-Globin Switching: Therapeutic Potential in β-Hemoglobinopathies

## TL;DR

This paper reviews how miRNAs regulate the switch from fetal to adult hemoglobin, offering potential therapies for β-hemoglobinopathies like sickle cell disease.

## Contribution

The paper highlights novel miRNA-mediated regulation and nanoparticle delivery strategies for reactivating fetal hemoglobin.

## Key findings

- miRNAs like miR-144 and miR-26b modulate hemoglobin switching by targeting transcription factors.
- Nanoparticle-based delivery systems show promise for therapeutic miRNA application in β-hemoglobinopathies.

## Abstract

Erythropoiesis is a tightly regulated developmental process that requires the switch from fetal hemoglobin (HbF) to adult hemoglobin (HbA). In β-hemoglobinpathies such as SCD and β-thalassemia, disease severity is influenced by the fetal-to-adult hemoglobin switch because persistence or induction of HbF will ameliorate the clinical manifestations. miRNAs play an essential role in regulating this switch by modulating the expression levels of key transcription factors, such as BCL11A, KLF1, and MYB, which repress γ-globin expression. Multiple miRNAs have been identified as potential modulators of the hemoglobin switch, including miR-144, miR-486, miR-26b, and miR-15a. The molecular interactions between miRNA and γ-to β-globin switch have the potential for new therapeutic interventions that aim to reactivate HbF expression to ameliorate β-hemoglobinopathies such as SCD and β-thalassemia. In this review, the latest advancements in miRNA-mediated regulation of Hb switching and nanoparticle-based strategies for miRNA delivery are explored.