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Characterization of a full-length infectious cDNA clone and a GFP reporter derivative of the oncolytic picornavirus SVV-001.
Poirier, John T; Reddy, P Seshidhar; Idamakanti, Neeraja; Li, Shawn S; Stump, Kristine L; Burroughs, Kevin D; Hallenbeck, Paul L; Rudin, Charles M.
Afiliação
  • Poirier JT; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
  • Reddy PS; Neotropix, Inc., 351 Phoenixville Pike, Malvern, PA 19355, USA.
  • Idamakanti N; Neotropix, Inc., 351 Phoenixville Pike, Malvern, PA 19355, USA.
  • Li SS; Neotropix, Inc., 351 Phoenixville Pike, Malvern, PA 19355, USA.
  • Stump KL; Neotropix, Inc., 351 Phoenixville Pike, Malvern, PA 19355, USA.
  • Burroughs KD; Neotropix, Inc., 351 Phoenixville Pike, Malvern, PA 19355, USA.
  • Hallenbeck PL; Neotropix, Inc., 351 Phoenixville Pike, Malvern, PA 19355, USA.
  • Rudin CM; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA.
J Gen Virol ; 93(Pt 12): 2606-2613, 2012 Dec.
Article em En | MEDLINE | ID: mdl-22971818
ABSTRACT
Seneca Valley virus (SVV-001) is an oncolytic picornavirus with selective tropism for a subset of human cancers with neuroendocrine differentiation. To characterize further the specificity of SVV-001 and its patterns and kinetics of intratumoral spread, bacterial plasmids encoding a cDNA clone of the full-length wild-type virus and a derivative virus expressing GFP were generated. The full-length cDNA of the SVV-001 RNA genome was cloned into a bacterial plasmid under the control of the T7 core promoter sequence to create an infectious cDNA clone, pNTX-09. A GFP reporter virus cDNA clone, pNTX-11, was then generated by cloning a fusion protein of GFP and the 2A protein from foot-and-mouth disease virus immediately following the native SVV-001 2A sequence. Recombinant GFP-expressing reporter virus, SVV-GFP, was rescued from cells transfected with in vitro RNA transcripts from pNTX-11 and propagated in cell culture. The proliferation kinetics of SVV-001 and SVV-GFP were indistinguishable. The SVV-GFP reporter virus was used to determine that a subpopulation of permissive cells is present in small-cell lung cancer cell lines previously thought to lack permissivity to SVV-001. Finally, it was shown that SVV-GFP administered to tumour-bearing animals homes in to and infects tumours whilst having no detectable tropism for normal mouse tissues at 1×10(11) viral particles kg(-1), a dose equivalent to that administered in ongoing clinical trials. These infectious clones will be of substantial value in further characterizing the biology of this virus and as a backbone for the generation of additional oncolytic derivatives.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Picornaviridae / Vírus Oncolíticos Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Picornaviridae / Vírus Oncolíticos Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2012 Tipo de documento: Article