Modification of globin gene expression by RNA targeting strategies.

Modification of globin gene expression by RNA targeting strategies. Research Abstract Details 

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Modification of globin gene expression by RNA targeting strategies. Abstract Text:

Tong-Jian Shen,Heather Rogers,Xiaobing Yu,Felix Lin,Constance T Noguchi,Chien Ho,

OBJECTIVE: Sickle cell anemia is a genetic blood disease resulting from production of mutant beta-globin (beta(S)) and has severe clinical consequences. It is known that a higher cellular gamma-globin level, e.g., higher ratio of cellular gamma-globin to beta(S)-globin (gamma/beta(S) ratio), inhibits sickle hemoglobin (HbS) polymerization tendency. Hence, therapeutic treatment of sickle cell anemia has been focused on introducing gamma-globin gene into red blood cells to increase the cellular gamma/beta(S) ratio. Here, we have introduced ribozymes and small interfering RNAs (siRNAs) against beta(S)-globin mRNA into blood cells as a means to increase the gamma/beta(S) ratio. MATERIALS AND METHODS: Single and multiribozymes against beta(S)-globin mRNA have been tested in vitro and in human erythroleukemia K562beta(S) cells that stably express exogenous beta(S)-globin gene. Primary human hematopoietic progenitor cells were also transfected with multiribozyme and the gamma/(gamma + beta) ratio determined and compared with cells transfected with long hairpin beta-globin cDNA and synthetic siRNA genes. RESULTS: We have found that the multiribozyme zb21A containing two ribozyme units effectively reduces beta(S)-globin mRNA both in vitro and in K562beta(S) cells. The gamma-globin mRNA to beta(S)-globin mRNA ratio in the multiribozyme transfected cells is about a factor of 2 more than that in the control cells. We have also found that the gamma/(gamma + beta) ratio in the transfected hematopoietic progenitor cells is increased by more than twofold in cells treated with multiribozyme zb21A or siRNA ib5. CONCLUSION: Our results suggest that introducing multiribozymes or siRNAs into red blood cells is comparable in their effectiveness to increase the ratio of cellular gamma-globin mRNA to beta- or beta(S)-globin mRNA, providing possible strategies to increase the effectiveness of gamma-globin gene transfer as gene therapy for treatment of patients with sickle cell anemia.

Modification of globin gene expression by RNA targeting strategies. Publishing Authors By Initials

TJ Shen,H Rogers,X Yu,F Lin,CT Noguchi,C Ho,

For similar nucleic acids, nucleotides, and nucleosides: antisense elements (genetics): rna, antisense: rna, small interfering research abstracts see: nucleic acids, nucleotides, and nucleosides: antisense elements (genetics): rna, antisense: rna, small interfering research

PUBMED ID PMID:

MEDLINE DATE:

Modification of globin gene expression by RNA targeting strategies. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Experimental hematology

VOLUME: 35

Page Numbers: 1209-18

Journal Abbreviation: Exp. Hematol.

ISSN: 0301-472X

DAY: 3

MONTH: Aug

YEAR: 2007

Modification of globin gene expression by RNA targeting strategies. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 402313

Modification of globin gene expression by RNA targeting strategies. Keywords Mesh Terms:

KEYWORDS: RNA, Small Interfering

MESH TERMS: genetics

Chemical & Substance for Abstract: Modification of globin gene expression by RNA targeting strategies. Information

Substance Name: Globins

Registry Number: 9004-22-2

Grant and Affiliation Information for Modification of globin gene expression by RNA targeting strategies.

AFFILIATION: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.

Country: Netherlands

AGENCY: United States NHLBI

GRANT: R01HL-024525

ACRONYM: HL

MEDLINETA: Exp Hematol

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