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Usage of U7 snRNA in gene therapy of hemoglobin S disorder--is it feasible?/ Hemoglobin S hastaliginin gen tedavisinde U7 snRNA kullanimi uygun mu?

Of several hemoglobinopathies, hemoglobin (Hb) S disorder [beta6(A3)Glu [right arrow] Val, GAG [right arrow] GTG] is one of the most common forms [1]. Similar to a thalassemia carrier, heterozygous Hb S without concomitant thalassemia is usually asymptomatic. For treatment of hemoglobinopathies, the new alternative is the usage of gene therapy. Recently, repair of defective splicing by small nuclear RNAs (SnRNAs), as a therapeutic agent, was proposed. This process involves replacement of the natural antisense sequence with that tackles to the desired RNA [2] and becomes a new modality in advanced gene therapy for hemoglobinopathies. This process allows for possible long-term expression of RNA antisense to its targets such as the aberrant thalassemic splice sites in beta globin RNA [2].

Here, the author performs a basic bioinformatic analysis to assess the effect of co-expression between nucleic acid sequence for human Hb S beta globin chain and U7.623. To answer the raised question, a gene ontology technique was applied. The database PubMed was used for data mining of the nucleic acid sequence for human beta globin chain, and then the mutation beta 6 was experimentally done to obtain the primary sequence in Hb S disorder. In addition, the modified U7 snRNA (U7.623) was also searched and used for further study. Later, the author performed prediction of molecular function and biological process for the combination between nucleic acid sequence for human Hb S beta globin chain and U7.623 using a novel gene ontology prediction tool, GoFigure, which accepts an input DNA or protein sequence, and uses BLAST to identify homologous sequences in gene ontology databases [3]. As a result, the molecular function and biological process in the co-expression between nucleic acid sequence for human Hb S beta globin chain and U7.623 was predicted as oxygen transporter activity for molecular function and oxygen transport for biological process, indicating complete recovery.

Gene therapy is a new therapeutic focus in modern medicine for many genetic diseases including hemoglobinopathy [2]. Concerning thalassemia, modified U7 snRNA [4] is a widely documented SnRNA for therapy for beta globin gene defect. Here, the author assessed the effect of co-expression between nucleic acid sequence for human Hb S beta globin chain and U7.623 by the standard published technique by Wiwanitkit [5]. According to this study, the gene ontological results showed that full recovery of hemoglobin in both molecular function and biological process can be achieved. Indeed, U7.623 antisense is already confirmed for its effectiveness in repairing gene therapy for several beta-thalassemia mutations [5-8]. However, there is a limited knowledge on Hb S disorder. This work is intended to extend our knowledge, and it implies the usefulness of this antisense approach to correct splicing defects in Hb S disorder. However, this is only a prediction that needs to be confirmed by in vitro analysis.

Received: December 13, 2007 Accepted: June 10, 2009


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[3.] Khan S, Situ G, Decker K, Schmidt CJ. GoFigure: automated Gene Ontology annotation. Bioinformatics 2003;19:2484-5.

[4.] Phillips SC, Turner PC. Nucleotide sequence of the mouse U7 snRNA gene. Nucleic Acids Res 1991;19:1344.

[5.] Wiwanitkit V. Usage of U7 snRNA in gene therapy of hemoglobin C disorder: feasibility by gene ontology tool. African J Biotechnol. 2007;6:683-4.

[6.] Gorman L, Suter D, Emerick V, Schumperli D, Kole R. Stable alteration of pre-mRNA splicing patterns by modified U7 small nuclear RNAs. Proc Natl Acad Sci U S A 1998;95:4929-34.

[7.] Suter D, Tomasini R, Reber U, Gorman L, Kole R, Schumperli D. Double-target antisense U7 snRNAs promote efficient skipping of an aberrant exon in three human b-thalassemic mutations. Human Mol Genet 1999;8:2415-23.

[8.] Suwanmanee T, Sierakowska H, Fucharoen S, Kole R. Repair of a splicing defect in erythroid cells from patients with b-thalassemia/ HbE disorder. Mol Ther 2002;6:718-26.

Address for Correspondence: Dr. Viroj Wiwanitkit, Wiwanitkit House, Bangkhae, 10160 Bangkok, Thailand Phone: 662-2564136 E-mail:

Viroj Wiwanitkit

Wiwanitkit House, Bangkhae, 10160 Bangkok , Thailand
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Title Annotation:small nuclear deoxyribonucleic acid
Author:Wiwanitkit, Viroj
Publication:Turkish Journal of Hematology
Article Type:Report
Geographic Code:9THAI
Date:Sep 1, 2009
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