E-MTAB-1636 - Transcription profiling by array of human 786-0 cells infected with MG1 and MG1-B19R viral strains to assess the impact of cloning an IFN decoy receptor isolated from vaccinia virus B19R on the transcriptional response against an IFN sensitive maraba virus strain MG1
Released on 1 June 2013, last updated on 3 May 2014
Oncolytic viruses are complex biological agents that interact at multiple levels with both tumor and normal tissues. Anti-viral pathways induced by interferon are known to play a critical role in determining tumor cell sensitivity and normal cell resistance to infection with oncolytic viruses. Here we pursue a synthetic biology approach to identify methods that enhance anti-tumor activity of oncolytic viruses through suppression of IFN signaling. Based on the mathematical analysis of multiple strategies, we hypothesize that a positive feedback loop, established by virus-mediated expression of a soluble interferon-binding decoy receptor, increases tumor cytotoxicity without compromising normal cells. Oncolytic rhabodviruses engineered to express a secreted interferon antagonist have improved oncolytic potential in cellular cancer models, and display improved therapeutic potential in tumor-bearing mice. Our results demonstrate the potential of this methodology in evaluating potential caveats of viral immune evasion strategies and improving the design of oncolytic viruses. The following series of microarray experiments was utilized to assess the impact of cloning an IFN decoy receptor isolated from vaccinia virus termed B19R on the transcriptional response against an IFN sensitive maraba virus strain termed MG1. RNA extraction was performed 24h post infection in 786-0 cells. Duplicate samples were pooled, and hybridized on Affymetrix human gene 1.0 ST arrays according to manufacturer instructions. Data analysis was performed using AltAnalyze. Briefly, probeset filtering implemented a DABG threshold of 70 & pV<0.05 and utilized exclusively constitutively expressed exons to assess levels of gene expression.
transcription profiling by array, disease state design
Model-based Rational Design of an Oncolytic Virus with Improved Therapeutic Potential. Fabrice Le Bœuf, Cory Batenchuk, Markus Vaha-Koskela, Sophie Breton, Dominic Roy, Chantal Lemay, Julie Cox, Hesham Abdelbary, Theresa Falls, Girija Waghray, Harold Atkins, David Stojdl, Jean-Simon Diallo, Mads Kaern, John Bell.