Efficient infection and persistence of a herpesvirus saimiri-based gene delivery vector into human tumor xenografts and multicellular spheroid cultures.
Herpesvirus saimiri (HVS) has the ability to infect a variety of human cell lines and establish a persistent infection by virtue of episomal maintenance. Moreover, the viral episome provides sustained expression of a heterologous transgene. HVS-based vectors can also persist for a long term in tumor xenografts generated from HVS-infected human carcinoma cell lines. The viral episome remains latent within the xenograft allowing long-term transgene expression. These properties, in addition to its ability to incorporate large amounts of heterologous DNA, make HVS an attractive potential gene delivery vector. Here we report on the further evaluation of such HVS-based vectors. We demonstrate for the first time that HVS can efficiently infect solid tumor xenografts derived from a variety of human carcinoma cells via direct intratumoral injections. Furthermore, HVS can efficiently infect spheroid cultures, a three-dimensional cell culture system that closely resembles a tumor. Upon infection of both the tumor xenografts and spheroid cultures, HVS-based vectors can establish a persistent episomal infection within the tumor xenograft allowing expression of a heterologous transgene. These results suggest that HVS-based vectors may be suitable for cancer gene therapy applications.
Smith
Peter G
PG
School of Biochemistry & Microbiology, University of Leeds, Leeds LS2 9JT, UK.
Burchill
Sue A
SA
Brooke
David
D
Coletta
P Louise
PL
Whitehouse
Adrian
A
D000818:Animals; D005260:Female; D005453:Fluorescence; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured