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Literature DB >> 10944225

Restoration of hemoglobin A synthesis in erythroid cells from peripheral blood of thalassemic patients.

G Lacerra¹, H Sierakowska, C Carestia, S Fucharoen, J Summerton, D Weller, R Kole.

Abstract

Mononuclear cells from peripheral blood of thalassemic patients were treated with morpholino oligonucleotides antisense to aberrant splice sites in mutant beta-globin precursor mRNAs (pre-mRNAs). The oligonucleotides restored correct splicing and translation of beta-globin mRNA, increasing the hemoglobin (Hb) A synthesis in erythroid cells from patients with IVS2-654/beta(E), IVS2-745/IVS2-745, and IVS2-745/IVS2-1 genotypes. The maximal Hb A level for repaired IVS2-745 mutation was approximately 30% of normal; Hb A was still detectable 9 days after a single treatment with oligonucleotide. Thus, expression of defective beta-globin genes was repaired and significant level of Hb A was restored in a cell population that would be targeted in clinical applications of this approach.

Entities: Chemical Disease Species

Mesh：

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Year: 2000 PMID： 10944225 PMCID： PMC16909 DOI： 10.1073/pnas.97.17.9591

Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205

29 in total

Review 1. Frequencies of common beta-thalassaemia alleles among different populations: variability in clinical severity.

Authors: T H Huisman
Journal: Br J Haematol Date: 1990-08 Impact factor: 6.998

2. Reversibility of IVS 2 missplicing in a mutant human beta-globin gene.

Authors: C Dobkin; A Bank
Journal: J Biol Chem Date: 1985-12-25 Impact factor: 5.157

3. RNA transcripts of the beta-thalassaemia allele IVS-2-654 C-->T: a small amount of normally processed beta-globin mRNA is still produced from the mutant gene.

Authors: S Z Huang; F Y Zeng; Z R Ren; Z H Lu; G P Rodgers; A N Schechter; Y T Zeng
Journal: Br J Haematol Date: 1994-11 Impact factor: 6.998

4. Specific transcription and RNA splicing defects in five cloned beta-thalassaemia genes.

Authors: R Treisman; S H Orkin; T Maniatis
Journal: Nature Date: 1983-04-14 Impact factor: 49.962

5. Abnormally spliced messenger RNA in erythroid cells from patients with beta+ thalassemia and monkey cells expressing a cloned beta+-thalassemic gene.

Authors: Y Fukumaki; P K Ghosh; E J Benz; V B Reddy; P Lebowitz; B G Forget; S M Weissman
Journal: Cell Date: 1982-03 Impact factor: 41.582

6. Beta + thalassemia: aberrant splicing results from a single point mutation in an intron.

Authors: M Busslinger; N Moschonas; R A Flavell
Journal: Cell Date: 1981-12 Impact factor: 41.582

7. beta-Thalassemia in Chinese: use of in vivo RNA analysis and oligonucleotide hybridization in systematic characterization of molecular defects.

Authors: T C Cheng; S H Orkin; S E Antonarakis; M J Potter; J P Sexton; A F Markham; P J Giardina; A Li; H H Kazazian
Journal: Proc Natl Acad Sci U S A Date: 1984-05 Impact factor: 11.205

8. Direct selection for mutations affecting specific splice sites in a hamster dihydrofolate reductase minigene.

Authors: I T Chen; L A Chasin
Journal: Mol Cell Biol Date: 1993-01 Impact factor: 4.272

9. Restoration of correct splicing in thalassemic pre-mRNA by antisense oligonucleotides.

Authors: Z Dominski; R Kole
Journal: Proc Natl Acad Sci U S A Date: 1993-09-15 Impact factor: 11.205

10. Isobutyramide, an orally bioavailable butyrate analogue, stimulates fetal globin gene expression in vitro and in vivo.

Authors: S P Perrine; G H Dover; P Daftari; C T Walsh; Y Jin; A Mays; D V Faller
Journal: Br J Haematol Date: 1994-11 Impact factor: 6.998

35 in total

Review 8. Alternative splicing and disease.

Authors: Jamal Tazi; Nadia Bakkour; Stefan Stamm
Journal: Biochim Biophys Acta Date: 2008-10-17

9. Antisense morpholino-oligomers directed against the 5' end of the genome inhibit coronavirus proliferation and growth.

Authors: Benjamin W Neuman; David A Stein; Andrew D Kroeker; Amy D Paulino; Hong M Moulton; Patrick L Iversen; Michael J Buchmeier
Journal: J Virol Date: 2004-06 Impact factor: 5.103

Review 10. Peptide-mediated cellular delivery of oligonucleotide-based therapeutics in vitro: quantitative evaluation of overall efficacy employing easy to handle reporter systems.

Authors: S D Laufer; T Restle
Journal: Curr Pharm Des Date: 2008 Impact factor: 3.116

Restoration of hemoglobin A synthesis in erythroid cells from peripheral blood of thalassemic patients.

Review 1. Frequencies of common beta-thalassaemia alleles among different populations: variability in clinical severity.

2. Reversibility of IVS 2 missplicing in a mutant human beta-globin gene.

3. RNA transcripts of the beta-thalassaemia allele IVS-2-654 C-->T: a small amount of normally processed beta-globin mRNA is still produced from the mutant gene.

4. Specific transcription and RNA splicing defects in five cloned beta-thalassaemia genes.

5. Abnormally spliced messenger RNA in erythroid cells from patients with beta+ thalassemia and monkey cells expressing a cloned beta+-thalassemic gene.

6. Beta + thalassemia: aberrant splicing results from a single point mutation in an intron.

7. beta-Thalassemia in Chinese: use of in vivo RNA analysis and oligonucleotide hybridization in systematic characterization of molecular defects.

8. Direct selection for mutations affecting specific splice sites in a hamster dihydrofolate reductase minigene.

9. Restoration of correct splicing in thalassemic pre-mRNA by antisense oligonucleotides.

10. Isobutyramide, an orally bioavailable butyrate analogue, stimulates fetal globin gene expression in vitro and in vivo.

1. Temperature-dependent splicing of beta-globin pre-mRNA.

Review 2. Therapeutic potential of antisense oligonucleotides as modulators of alternative splicing.

3. Future alternative therapies for β-thalassemia.

Review 4. Therapeutic potential of splice-switching oligonucleotides.

5. Sodium Butyrate and Valproic Acid as Splicing Restoring Agents in Erythroid Cells of β-Thalassemic Patients.

Review 6. Repair of pre-mRNA splicing: prospects for a therapy for spinal muscular atrophy.

Review 7. Approaches to Validate and Manipulate RNA Targets with Small Molecules in Cells.

Review 8. Alternative splicing and disease.

9. Antisense morpholino-oligomers directed against the 5' end of the genome inhibit coronavirus proliferation and growth.

Review 10. Peptide-mediated cellular delivery of oligonucleotide-based therapeutics in vitro: quantitative evaluation of overall efficacy employing easy to handle reporter systems.