Inhibition of α-globin gene expression by RNAi

Sarakul, Orawan; Vattanaviboon, Paiboon; Wilairat, Prapon; Fucharoen, Suthat; Abe, Yasunobu; Muta, Koichiro

doi:10.1016/j.bbrc.2008.02.124

Cited by 8 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[86][87][88] It appears though, that delivery of effector molecules may prove problematic and given that α-globin mRNA is highly expressed, this may not represent the ideal target. However, there are certain key differences between α-globin and β-globin expression which may reveal other avenues of intervention.…”

Section: Discussionmentioning

confidence: 99%

Controlling -globin: a review of -globin expression and its impact on -thalassemia

Voon¹,

Vadolas²

2008

Haematologica

View full text Add to dashboard Cite

Synthesis of α-globin and α-globin subunits of hemoglobin occurs at high levels during erythrocyte differentiation in a tightly controlled and co-ordinated fashion. Expression of α-globin is a fascinatingly complex process which has been meticulously defined in several recent studies, from chromatin modifications to Pol II recruitment. Following this, α-globin transcripts are processed and stabilized by a protein complex which binds the 3' untranslated region. Transcription and stabilization contribute to high level expression of α-globin. However, translation of α-globin at levels exceeding α-globin expression damages cellular membranes and results in β-thalassemia. It is, therefore, crucial that α-globin proteins are properly folded and stabilized, processes which are dependent on the presence of haem and AHSP. The exceedingly well-characterized process of α-globin expression elegantly illustrates the complex interaction of factors which are required to balance necessary high expression against the negative impacts of overexpression.

show abstract

Section: Discussionmentioning

confidence: 99%

Controlling -globin: a review of -globin expression and its impact on -thalassemia

Voon¹,

Vadolas²

2008

Haematologica

View full text Add to dashboard Cite

show abstract

“…The siRNA also reduced the number of hemoglobinized cells in erythroid colony-forming cells (ECFCs). 13 Moreover, an in vivo experiment in Hbb th−4 mice, in which the murine adult β globin gene was replaced by the human β IVS2−654 -globin gene, showed that intravenous injection of siRNA targeting α-globin sequence and antisense oligonucleotides targeting β-globin sequence improved red cell pathology, such as decreasing the nucleated cells in the bone marrow, increasing reticulocytes number 15 and increasing the survival rate of homozygous Hbb th−4 /Hbb th−4 and heterozygous Hbb/Hbbth−4. 14 …”

Section: Nucleic Acid Therapy For β-Thalassemiamentioning

confidence: 99%

<p>Nucleic Acid Therapy for β-Thalassemia</p>

d'Arqom¹

2020

BTT

View full text Add to dashboard Cite

β-thalassemia is caused by mutations in the β-globin gene which diminishes or abolishes β-globin chain production. This reduction causes an imbalance of the α/β-globin chain ratio and contributes to the pathogenesis of the disease. Several approaches to reduce the imbalance of the α/β ratio using several nucleic acid-based technologies such as RNAi, lentiviral mediated gene therapy, splice switching oligonucleotides (SSOs) and gene editing technology have been investigated extensively. These approaches aim to reduce excess free α-globin, either by reducing the α-globin chain, restoring β-globin expression and reactivating γ-globin expression, leading a reduced disease severity, treatment necessity, treatment interval, and disease complications, thus, increasing the life quality of the patients and alleviating economic burden. Therefore, nucleic acid-based therapy might become a potential targeted therapy for β-thalassemia.

show abstract

“…RNA interference technology could offer advantage in gene therapy approach by silencing the alpha globin gene to reduce the alpha globin levels and restore normal ratio between alpha and beta globin chains [62]. Correction of the mutant phenotype at the level of mRNA could be also approached, by using chemically stabilized antisense oligonucleotides [60,63].…”

Section: Genetic and Metabolic Erds And Current Treatmentmentioning

confidence: 99%

The Potential Role of Cell Penetrating Peptides in the Intracellular Delivery of Proteins for Therapy of Erythroid Related Disorders

Papadopoulou

Tsiftsoglou

2013

Pharmaceuticals

View full text Add to dashboard Cite

The erythroid related disorders (ERDs) represent a large group of hematological diseases, which in most cases are attributed either to the deficiency or malfunction of biosynthetic enzymes or oxygen transport proteins. Current treatments for these disorders include histo-compatible erythrocyte transfusions or allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy delivered via suitable viral vectors or genetically modified HSCs have been under way. Protein Transduction Domain (PTD) technology has allowed the production and intracellular delivery of recombinant therapeutic proteins, bearing Cell Penetrating Peptides (CPPs), into a variety of mammalian cells. Remarkable progress in the field of protein transduction leads to the development of novel protein therapeutics (CPP-mediated PTs) for the treatment of monogenetic and/or metabolic disorders. The “concept” developed in this paper is the intracellular protein delivery made possible via the PTD technology as a novel therapeutic intervention for treatment of ERDs. This can be achieved via four stages including: (i) the production of genetically engineered human CPP-mediated PT of interest, since the corresponding native protein either is missing or is mutated in the erythroid progenitor cell (ErPCs) or mature erythrocytes of patients; (ii) isolation of target cells from the peripheral blood of the selected patients; (iii) ex vivo transduction of cells with the CPP-mediated PT of interest; and (iv) re-administration of the successfully transduced cells back into the same patients.

show abstract

Inhibition of α-globin gene expression by RNAi

Cited by 8 publications

References 20 publications

Controlling -globin: a review of -globin expression and its impact on -thalassemia

Controlling -globin: a review of -globin expression and its impact on -thalassemia

<p>Nucleic Acid Therapy for β-Thalassemia</p>

The Potential Role of Cell Penetrating Peptides in the Intracellular Delivery of Proteins for Therapy of Erythroid Related Disorders

Contact Info

Product

Resources

About