RNA Silencing: An Approach for the Treatment of ÃÂ²-Thalassemia

Urkude Vikas,Mishra Amit

doi:10.4172/2157-7013.1000135

Abstract

Thalassemia is an inherited disorder of blood, which is passed from one generation to another, represents the most common hemoglobinopathies caused. It occurs due to reduce or minute production of hemoglobin. Augmented levels of fetal hemoglobin (HbF) can revolutionize the severity of the β-hemoglobin disorders, like β-thalassemia. More recently, major advances have been made in the discovery of critical modifier genes, such as BCL11A (B cell lymphoma 11A), a master regulator of HbF (fetal hemoglobin) and hemoglobin switching. Down regulation of BCL11A expression or function by siRNA or small molecules may offer a new therapeutic approach to directed activation of HbF in adult erythroid cells of patients with β-thalassemia and other disorders of β-hemoglobin. RNA interference (RNAi) is a commonly used procedure for the analysis of regulation of gene expression in a variety of cells, by which target messenger RNA (mRNA) is cleaved by small interfering complementary RNA (siRNA). RNA silencing with direct delivery of siRNA can be used to suppress BCL11A gene expression. This review discusses the role of globin gene regulation in thalassemia, RNAi interference and related approaches available for the treatment of thalassemia major patients.

Highlights

The thalassemias are worldwide genetic disorders that result in defective globin-chain production as a consequence of a large number of different genetic lesions [1]
This variation in expression appears to have an effect on the function of BCL11A at the human γ-globin locus, where it is considered to act with the erythroid transcription factors GATA-1 and FOG-1, as well as the NuRD remodeling and repressor complex to silence the γ-globin genes [12]
In earlier studies it was found that BCL11A maintains silencing of γ-globin expression in adult erythroid cells and functions as a direct transcriptional regulator of the fetal to adult hemoglobin switch in humans [13]

Summary

Introduction

The thalassemias are worldwide genetic disorders that result in defective globin-chain production as a consequence of a large number of different genetic lesions [1]. Beta thalassemia β-thalassemia, one of the most common single gene disorders, results from the decreased production of β-globin chains. This variation in expression appears to have an effect on the function of BCL11A at the human γ-globin locus, where it is considered to act with the erythroid transcription factors GATA-1 and FOG-1, as well as the NuRD remodeling and repressor complex to silence the γ-globin genes [12].

Results

Conclusion