title: Establishment of a novel foreign gene delivery system combining an HSV amplicon with an attenuated replication-competent virus, HSV-1 HF10.
abstract: Herpes simplex virus type 1 (HSV-1)-based amplicon vectors have been used widely in genetic engineering with many advantages for gene delivery, being easily constructed. An attenuated and replication-competent HSV-1 HF10 clone demonstrating an oncolytic effect on cancer cells in vitro and in vivo has been applied recently for clinical virotherapy of breast cancers and the present studies were conducted to test its efficacy in combination with an HSV-1 amplicon. For this purpose, a new system was developed to produce high titers of the HSV-1 amplicon vector and the results showed that its package efficiency and the titer ratio to HF10 were improved by passage through two cell lines. A high ratio of amplicon/helper virus HF10 (A/H) (>1) was required to express the foreign gene efficiently. Furthermore, in order to express the foreign gene conditionally, an HSV-1 ICP8 promoter was introduced in place of the human cytomegalovirus MIE promoter, this driving expression of the transgene when replication of HF10 progressed. The methodology for simple preparation of mixtures of viruses containing the amplicon with the oncolytic virus is documented. This system should find application for studies of cancer therapy.
authors.affiliation: Division of Virology, Aichi Cancer Center Research Institute, 1-1, Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
authors.forename: Lumin
authors.initials: L
authors.lastname: Zhang
authors.forename: Tohru
authors.initials: T
authors.lastname: Daikoku
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohtake
authors.forename: Junpei
authors.initials: J
authors.lastname: Ohtsuka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nawa
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kudoh
authors.forename: Satoko
authors.initials: S
authors.lastname: Iwahori
authors.forename: Hiroki
authors.initials: H
authors.lastname: Isomura
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Nishiyama
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Tsurumi
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006378:Helper Viruses / Q000502:physiology; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D050504:Oncolytic Viruses / Q000502:physiology; D011995:Recombination, Genetic; D014779:Virus Replication