Figure 7.
Schematic representation of HIV-1–based, lentiviral globin expression cassettes utilized to correct murine models of β-thalassemia and sickle cell disease. The mLARβΔγV5 globin expression cassette is compared with those contained in TNS9, βA-T87Q, and βAS.31,2,5 DNA fragments containing the HS sites and flanking sequences appear as open horizontal rectangles, the solid horizontal arrow indicates the β-globin promoter, and the hatched horizontal arrows indicate the genomic β- or γ-globin sequences contained in the mature mRNA. The solid lines connecting the 3 arrows represent intronic sequences; all of the vectors utilized a deletion in intron 2 to improve vector performance. The solid gray rectangle indicates the 3′β-globin enhancer sequence. The fragment sizes of the DNA elements derived from the β-globin LCR that contain the indicated HS sites are shown below each horizontal rectangle, whereas the GenBank coordinates (accession number U01317) of the sequences are shown above each rectangle.