title: Towards β-globin gene-targeting with integrase-defective lentiviral vectors.
abstract: 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.
authors.affiliation: National Institute of Genetic Engineering & Biotechnology, Tehran, Iran.
authors.forename: Davoud Nouri
authors.initials: DN
authors.lastname: Inanlou
authors.forename: Bagher
authors.initials: B
authors.lastname: Yakhchali
authors.forename: Hossein
authors.initials: H
authors.lastname: Khanahmad
authors.forename: Mossa
authors.initials: M
authors.lastname: Gardaneh
authors.forename: Hesam
authors.initials: H
authors.lastname: Movassagh
authors.forename: Reza Ahangari
authors.initials: RA
authors.lastname: Cohan
authors.forename: Mehdi Shafiee
authors.initials: MS
authors.lastname: Ardestani
authors.forename: Reza
authors.initials: R
authors.lastname: Mahdian
authors.forename: Sirous
authors.initials: S
authors.lastname: Zeinali
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000201:enzymology; D006921:Hygromycin B / Q000031:analogs & derivatives / Q000494:pharmacology; D019426:Integrases / Q000172:deficiency; D016086:Lentivirus / Q000235:genetics*; D009355:Neomycin / Q000494:pharmacology; D011995:Recombination, Genetic; D012641:Selection, Genetic; D017385:Sequence Homology; D013937:Thymidine Kinase / Q000378:metabolism; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000628:therapy
chemical_list: D000900:Anti-Bacterial Agents; D002934:Cinnamates; D055544:beta-Globins; D006921:Hygromycin B; C026273:hygromycin A; D013937:Thymidine Kinase; D019426:Integrases; D009355:Neomycin