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. 2021 Aug 2;13(8):1526. doi: 10.3390/v13081526

Figure 1.

Figure 1

Schematic representation of HIV-1-derived lentiviral vectors (LVs) used in clinical applications of gene therapy for monogenic diseases. (A) A prototype, third-generation LV provirus, featuring a disabling (SIN) deletion of the enhancer/promoter sequences in the U3 region of the long terminal repeat (LTR) up to position -18 from the viral transcription start site. The enlarged portion of the LTR shows the original arrangement of the transcription factor binding sites and TATA box in the HIV-1 U3 region, deleted in the LV LTR. The poly(A) signal-containing R and the U5 regions of the LTR are retained. PBS, primer binding site; ΔGAG, deleted, non-coding portion of the GAG gene containing the D1 major HIV-1 splice donor (SD) site (CTG/GTGAGTAC); RRE, Rev-responsive element; ΔENV, deleted portion of the ENV gene containing the A7 HIV-1 splice acceptor (SA) site (TCGTTTCAG/A); cPPT, central polypurine tract; E/P, enhancer/promoter component of the expression cassette (the arrow represents the transcription start site); WPRE, woodchuck hepatitis virus post-transcriptional regulatory element; Ψ, extended packaging signal. (B) 1 to 10, schematic composition of the LVs described in the text. MND, modified enhancer/promoter of the murine myeloproliferative sarcoma virus; ABCD1, ATP-binding cassette, subfamily D, member 1 cDNA; EF1α, short promoter of the elongation factor 1α gene; ADA, Adenosine deaminase cDNA; W, WPRE; PGK, phosphoglycero kinase gene promoter; ARSA, arylsulfatase cDNA; WASPp, 1.6-kb extended Wiskott-Aldrich protein gene promoter; WASP, Wiskott-Aldrich protein cDNA; CTSG-cFES, hybrid promoter containing cFES regulatory regions and CTSG promoter. GP91, Gp91phox cDNA; MSP, myeloid-specific promoter; 126T (2×) tandem repeat of the miR-126 binding site; ET, liver-specific transthyretin promoter/enhancer; FIX, coagulation factor IX cDNA; 142T (4×) tetrameric repeat of the miR-142 binding site; E3, E2, E1, exons 3, 2 and 1 of the human β-globin gene; βp, human β-globin gene promoter; HS2, HS3, HS4, hypersensitive site 2, 3 and 4 regions of the β-globin locus-control region; 3′ Enh, 3′ enhancer of the human β-globin gene. T87Q, codon substitution causing a tryptophan to glutamine amino acid substitution at position 87 of the β-globin protein; miRNA, gene encoding a shRNA/miR hybrid small nuclear RNA targeting the BCL11A transcription factor mRNA.