RNA therapeutics for β-thalassemia.

Abstract

β-thalassemia is an autosomal recessive disease, caused by one or more mutations in the β-globin gene that reduces or abolishes β-globin chain synthesis causing an imbalance in the ratio of α- and β-globin chain. Therefore, the ability to target mutations will provide a good result in the treatment of β-thalassemia. RNA therapeutics represents a promising class of drugs inclusive antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and APTAMER have investigated in clinical trials for treatment of human diseases as β-thalassemia; Especially, ASO therapeutics can completely treat β-thalassemia patients by the way of making ASO infiltrating through erythrocyte progenitor cells, migrating to the nucleus and hybridizing with abnormal splicing sites to suppress an abnormal splicing pattern of β-globin pre-mRNA. As a result, the exactly splicing process is restored to increase the expression of β-globin which increases the amount of mature hemoglobin of red blood cells of β-thalassemia patients. Furthermore, current study demonstrates that RNA-based therapeutics get lots of good results for β-thalassemia patients. Then, this chapter focuses on current advances of RNA-based therapeutics and addresses current challenges with their development and application for treatment of β-thalassemia patients.