Fig. 1
From: Gene Transfer into Hepatocytes Mediated by Helper Virus-Free HSV/AAV Hybrid Vectors
Schematic diagram of HSV-1 amplicon and HSV/AAV hybrid vectors
(A) pHSVmG6Pase contains the mouse glucose-6-phosphatase cDNA (mG6Pase) under control of the HSV-1 immediate-early 4/5 promoter (IE 4/5 prom). (B—G) Amplicon vectors that contain the lacZ reporter gene under transcriptional control of either (B) the IE 4/5 promoter (pHSVlac) or the liver-specific (C) human apolipoprotein E enhancer (hpaoE enh)/human α1-antitrypsin promoter (hAAT prom; papoEhAATlac/i), (D and E) the mouse albumin promoter (malb prom; pmalblac/i and pmalblac), or (F and G) the mouse albumin enhancer (malb enh, malb enh inv) and promoter (pmalbe/placa and pmalbe/placb). Two of the constructs (papoEhAATlac/i and pmalblac/i) contain the α-globin intron (intr) downstream of the lacZ open reading frame. (H) pHSvGN contains a transgene cassette consisting of the green fluorescent protein cDNA (gfp) under control of the cytomegalovirus immediate-early 1 enhancer/promoter (cmv IE1 e/prom) and the neomycin phosphotransferase cDNA (neo) under control of the SV40 early promoter (SV40 E prom). (I) HSV/AAV hybrid vector pHYRGN contains the adeno-associated virus (AAV) rep gene and the AAV inverted terminal repeats (ITR) that flank the same transgene cassette as in pHSvGN. All vectors contain the HSV-1 origin of DNA replication (HSV-1 oris) and the DNA cleavage/packaging signal (HSV-1 pac) to support replication and packaging into HSV-1 virions in the presence of helper functions. Because the HSV-1 IE 4/5 promoter overlaps with oris sequences, three copies of the SV40 polyadenylation signal (tri-polyA) were inserted upstream of the liver-specific promoter elements (41). The positions of the SV40 polyA signals that terminate transcription of the lacZ and neo genes, and the bovine growth hormone (bGH) polyA signal that terminates transcription of the gfp gene, are indicated.