Herpesvirus saimiri-based vector biodistribution using noninvasive optical imaging.
Herpesvirus saimiri (HVS) is capable of infecting a range of human cell types with high efficiency and the viral genome persists as high copy number, circular, nonintegrated episomes which segregate to progeny upon cell division. This allows the HVS-based vector to stably transduce a dividing cell population and provide sustained transgene expression for an extended period of time both in vitro and in vivo. Here we assess the dissemination of HVS-based vectors in vivo following intravenous and intraperitoneal administration. Bioluminescence imaging of an HVS-based vector expressing luciferase demonstrates that the virus can infect and establish a persistent latent infection in a variety of mouse tissues. Moreover, the long-term in vivo maintenance of the HVS genome as a nonintegrated circular episome provided sustained expression of luciferase over a 10-week period. A particularly high level of transgene expression in the liver and the ability of HVS to infect and persist in hepatic stellate cells suggest that HVS-based vectors may have potential for the treatment of inherited and acquired liver diseases.
Smith
P G
PG
School of Biochemistry & Microbiology, University of Leeds, Leeds, UK.
Oakley
F
F
Fernandez
M
M
Mann
D A
DA
Lemoine
N R
NR
Whitehouse
A
A
D000818:Animals; D004247:DNA / Q000032:analysis*; D015870:Gene Expression; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics*; D007150:Immunohistochemistry / Q000379:methods; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008099:Liver / Q000201:enzymology / Q000821:virology*; D008107:Liver Diseases / Q000628:therapy; D008156:Luciferases / Q000235:genetics*; D049449:Luminescence; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014018:Tissue Distribution; D019076:Transgenes; D017735:Virus Latency
D004247:DNA; D008156:Luciferases