Yaba-like disease virus: an alternative replicating poxvirus vector for cancer gene therapy.
Vaccinia virus is being investigated as a replicating vector for tumor-directed gene therapy. However, the majority of cancer patients have preformed immunologic reactivity against vaccinia virus, as a result of smallpox vaccination, which may limit its use as a vector. The Yaba-like disease (YLD) virus was investigated here as an alternative, replicating poxvirus for cancer gene therapy. We have demonstrated that the YLD virus does not cross-react with vaccinia virus antibodies, and it replicates efficiently in human tumor cells. YLD virus can be expanded and purified to high titer in CV-1 cells under conditions utilized for vaccinia virus. The YLD virus RNA polymerase was able to express genes regulated by a synthetic promoter designed for use in orthopoxviruses. We sequenced the YLD virus TK gene and created a shuttle plasmid, which allowed the recombination of the green fluorescent protein (GFP) gene into the YLD virus. In a murine model of ovarian cancer, up to 38% of cells in the tumor expressed the GFP transgene 12 days after intraperitoneal virus delivery. YLD virus has favorable characteristics as a vector for cancer gene therapy, and this potential should be explored further.
Hu
Y
Y
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Lee
J
J
McCart
J A
JA
Xu
H
H
Moss
B
B
Alexander
H R
HR
Bartlett
D L
DL
D000818:Animals; D003429:Cross Reactions; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000628:therapy*; D011212:Poxviridae / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D011401:Promoter Regions, Genetic; D014616:Vaccinia virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D014779:Virus Replication