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- Title
959. Tumor Therapy Via Vector-Regulated Expression of Mutant Sodium Channel.
- Authors
Tannous, Bakhos A.; Perry, Katherine F.; Sena-Esteves, Miguel; Garcias-Anoveros, Jaime; Jacobs, Andreas; Corey, David P.; Weissleder, Ralph; Breakefield, Xandra O.
- Abstract
Viral vectors provide a means to deliver therapeutic genes to tumors on site. In this study, we describe a novel tumor therapy employing a dominant-negative mutant form of a mammalian brain sodium channel, BNac1. This channel was delivered to tumor cells using an HSV amplicon vector in which gene expression is controlled by a tetracycline regulatory system (tet-on) with silencer elements. Channel activity, regulated transgene expression, cell death and the bystander effect were evaluated in glioma cells in culture. Upon infection and drug induction, the constitutively open channel is expressed leading to sodium and water influx into cells with swelling and death (Fig. 1). Gap junctions were demonstrated between tumor cells and mediated a bystander effect by ion influx whereby non-infected tumor cells adjacent to infected tumor cells were also killed. Growth and therapeutic response in culture and in vivo were monitored, in real-time, in experimental tumors expressing a recently characterized Gaussia luciferase that is far more sensitive than other luciferases currently in use.Molecular Therapy (2006) 13, S370–S370; doi: 10.1016/j.ymthe.2006.08.1051
- Subjects
GENETIC vectors; TUMORS; SODIUM channels; ION channels; BRAIN
- Publication
Molecular Therapy, 2006, Vol 13, pS370
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.1051