Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sickle cell anemia is the most common heritable hematological disease, yet no curative treatment exists for this disorder. Moreover, the intricacies of globin gene expression have made the development of treatments for hemoglobinopathies based on gene therapy difficult. An alternative genetic approach to sickle cell therapy is based on RNA repair. A trans-splicing group I ribozyme was used to alter mutant beta-globin transcripts in erythrocyte precursors derived from peripheral blood from individuals with sickle cell disease. Sickle beta-globin transcripts were converted into messenger RNAs encoding the anti-sickling protein gamma-globin. These results suggest that RNA repair may become a useful approach in the treatment of genetic disorders.
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PMID:Ribozyme-mediated repair of sickle beta-globin mRNAs in erythrocyte precursors. 961 20

The beta-thalassemias and sickle cell anemia are severe congenital anemias for which there is presently no curative therapy other than allogeneic bone marrow transplantation. This therapeutic option, however, is not available to most patients due to the lack of an HLA-matched bone marrow donor. Emerging modalities based on cell engineering offer new prospects for potentially curative approaches that are applicable to more patients. The first is based on the transfer of a regulated globin gene in autologous hematopoietic stem cells (HSCs). This strategy, simple in principle, raises major challenges in terms of controlling transgene expression, which ideally should be erythroid-specific, differentiation and stage-restricted, elevated, position-independent, and sustained over time. Following the original report by May et al., several groups have reported that lentiviral vectors encoding slightly different combinations of proximal and distal transcriptional control elements of the normal human beta-globin gene permit lineage-specific and elevated beta-globin expression in vivo, resulting in therapeutic hemoglobin production and correction of anemia in beta-thalassemic mice. Clinical studies utilizing the TNS.3 vector are likely to be initiated in the US in 2009. While the addition of the wild-type beta-globin gene is naturally suited for treating beta-thalassemia, several alternatives have been proposed for the treatment of sickle cell disease, using either gamma- or mutant beta-globin gene addition, trans-splicing or RNA interference. The recent discovery that adult somatic cells can be reprogrammed to become pluripotent stem cells from which HSCs can be derived, provides yet another venue for developing stem cell engineering using either lentiviral vectors or homologous recombination techniques. Altogether, these recent advances bode well for the advent of curative stem cell-based therapies.
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PMID:Stem cell engineering for the treatment of severe hemoglobinopathies. 1899 54