Towards β-globin gene-targeting with integrase-defective lentiviral vectors.
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.
Inanlou
Davoud Nouri
DN
National Institute of Genetic Engineering & Biotechnology, Tehran, Iran.
Yakhchali
Bagher
B
Khanahmad
Hossein
H
Gardaneh
Mossa
M
Movassagh
Hesam
H
Cohan
Reza Ahangari
RA
Ardestani
Mehdi Shafiee
MS
Mahdian
Reza
R
Zeinali
Sirous
S
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
D000900:Anti-Bacterial Agents; D002934:Cinnamates; D055544:beta-Globins; D006921:Hygromycin B; C026273:hygromycin A; D013937:Thymidine Kinase; D019426:Integrases; D009355:Neomycin