Figure 2.

Lentivirus Vector Employed in Globin Gene Therapy

The diagram on top depicts the human β-globin gene locus, which consists of five genes (green boxes) that are expressed in a developmental stage-specific manner. High-level expression of the adult β-globin gene is mediated by the LCR HSs and the β-globin 3′ enhancer (blue ovals). Functional elements within all lentivirus vector systems include the long-terminal repeats (LTRs; gray boxes), splicing acceptor (SA) and donor (SD) sites, and the rev-responsive element (RRE), a structured RNA required for efficient viral replication. The TNS9 vector contains large segments of LCR elements HS2, HS3, and HS4, a wild-type β-globin gene, and a β-globin 3′enhancer. The HPV569 vector is similar to the TNS9 vector but contains a mutant β-globin gene that encodes a protein with a T to Q substitution at position 87. In addition, this vector contains two copies of the chicken HS4 (cHS4) insulator sequence in the LTRs. The Lenti-βAS3-FB vector is similar to HPV569 but expresses a β-globin protein with three amino acid substitutions (AS3) and contains single FB insulators in the LTRs. The GLOBE vector contains the β-globin gene and two large segments of the LCR (HS2 and HS3).