Herpes simplex virus type 1 thymidine kinase sequence fused to the lacz gene increases levels of {beta}-galactosidase activity per genome of high-capacity but not first-generation adenoviral vectors in vitro and in vivo.
Increased transgene expression per vector genome is an important goal in the optimization of viral vectors for gene therapy. Herein we demonstrate that herpes simplex virus type 1 (HSV1) thymidine kinase (TK) gene sequences (1,131 bp) fused to the 3' end of lacZ increase transgene expression from high-capacity adenoviral vectors (HCAd), but not from first-generation (Ad) vectors. The woodchuck hepatitis virus posttranscriptional regulatory element (WPRE), in contrast, increased transgene expression levels from Ad but not HCAd vectors. The differential activity of the HSV1 TK gene and WPRE sequences was detected both in vitro and in vivo and suggests potentially different mechanisms of action or the interaction of these elements with vector genomic sequences.
Puntel
M
M
Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Department of Medicine, University of California Los Angeles, 90048, USA.
Barrett
R J
RJ
Mondkar
S
S
Saxena
V
V
Kroeger
K M
KM
Muhammad
A K M
AK
Liu
C
C
Bondale
N
N
Sciascia
S
S
Xiong
W
W
Shi
Y
Y
Salem
A
A
Zadmehr
A
A
Huynh
P
P
Palmer
D
D
Ng
P
P
Castro
M G
MG
Lowenstein
P R
PR
D000256:Adenoviridae / Q000235:genetics*; D015870:Gene Expression; D005822:Genetic Vectors; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism*; D001616:beta-Galactosidase / Q000235:genetics* / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; D013937:Thymidine Kinase; D001616:beta-Galactosidase