The lentivirus vector use for the correction of sickle cell in transgenic mice.
Diagram of the βT27Q-globin provirus.
Abbreviations: HIV LTR, human immune deficiency type-1 virus long terminal repeat; +, packaging signal; cPPT/flap or central polypurine tract/DNA flap; RRE or Rev-responsive element; P, β-globin promoter; ppt, polypurine tract.
The 3′ β-globin enhancer, the 372 bp IVS2 deletion, the βT87Q mutation and sections of DnaseI hypersensitive sites (HS) 2, HS3, and HS4 of the β-globin LCR are indicated.
The cPPT/flap and the RRE element help in the export of the mRNA from the nucleus to the cytoplasma.
This vector integrates with an average of 3 copies per genome that is higher than previous vectors.
This vector has given no indication of silencing over time.
Reprinted with permission from
Abbreviations: LCR, locus control region, 5′ to the β-like gene cluster, involved in the development-appropriate globin gene expression; IVS2, intervening sequence 2.