A preclinical approach for gene therapy of β-thalassemia Conference Paper
| Authors: | Breda, L.; Kleinert, D. A.; Casu, C.; Casula, L.; Cartegni, L.; Fibach, E.; Mancini, I.; Giardina, P. J.; Gambari, R.; Rivella, S. |
| Title: | A preclinical approach for gene therapy of β-thalassemia |
| Conference Title: | 9th Cooley's Anemia Symposium |
| Abstract: | Lentiviral-mediated β-globin gene transfer successfully treated β-thalassemic mice. Based on this result, clinical trials were initiated. To date, however, no study has investigated the efficacy of gene therapy in relation to the nature of the different β-globin mutations found in patients. Most mutations can be classified as β0 or β+, based on the amount of β-globin protein produced. Therefore, we propose that a screening in vitro is necessary to verify the efficacy of gene transfer prior to treatment of individual patients. We used a two-phase liquid culture system to expand and differentiate erythroid progenitor cells (ErPCs) transduced with lentiviral vectors. We propose the use of this system to test the efficiency of lentiviral vectors carrying the human β-globin gene, to correct the phenotype of ErPCs from patients preparing for gene therapy. This new approach might have profound implications for designing gene therapy and for understanding the genotypephenotype variability observed in Cooley's anemia patients. © 2010 New York Academy of Sciences. |
| Keywords: | gene mutation; mutation; drug efficacy; drug safety; nonhuman; conference paper; medical decision making; animals; mice; cells, cultured; mus; stem cell factor; gene expression; erythropoietin; anemia; hemoglobin; gene transfer; genetic vectors; stem cell; cell culture; gene therapy; lentivirus; beta thalassemia; erythroid cell; transgene; beta-globins; beta-thalassemia; cyclosporin a; glutamine; lentivirinae; lentiviral vectors; thalassemia major; beta globin; β-globin; β-thalassemia; erythroid progenitor cells; phosphoglycerate dehydrogenase; streptomycin |
| Journal Title | Annals of the New York Academy of Sciences |
| Volume: | 1202 |
| Conference Dates: | 2009 Oct 21-24 |
| Conference Location: | New York, NY |
| ISBN: | 0077-8923 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2010-08-01 |
| Start Page: | 134 |
| End Page: | 140 |
| Language: | English |
| DOI: | 10.1111/j.1749-6632.2010.05594.x |
| PUBMED: | 20712784 |
| PROVIDER: | scopus |
| PMCID: | PMC3068625 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: ANYAA" - "Source: Scopus" |
