hygromycin-a and beta-Thalassemia

We have developed an integrase-defective lentiviral (LV) vector in combination with a gene-targeting approach for gene therapy of β-thalassemia. The β-globin gene-targeting construct has two homologous stems including sequence upstream and downstream of the β-globin gene, a β-globin gene positioned between hygromycin and neomycin resistant genes and a herpes simplex virus type 1 thymidine kinase (HSVtk) suicide gene. Utilization of integrase-defective LV as a vector for the β-globin gene increased the number of selected clones relative to non-viral methods. This method represents an important step toward the ultimate goal of a clinical gene therapy for β-thalassemia.

Topics: Anti-Bacterial Agents; beta-Globins; beta-Thalassemia; Cinnamates; Gene Targeting; Genetic Therapy; Genetic Vectors; Herpesvirus 1, Human; Hygromycin B; Integrases; Lentivirus; Neomycin; Recombination, Genetic; Selection, Genetic; Sequence Homology; Thymidine Kinase