Myeloma xenograft destruction by a nonviral vector delivering oncolytic infectious nucleic acid

Elizabeth M. Hadac, Elizabeth J. Kelly, Stephen J Russell

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The feasibility of using a nonviral vector formulation to initiate an oncolytic viral infection has not been previously demonstrated. We therefore sought to determine whether infectious nucleic acid (INA) could be used in place of virus particles to initiate an oncolytic picornavirus infection in vivo. Infectious RNA encoding coxsackievirus A21 (CVA21) was transcribed from plasmid DNA using T7 polymerase. Within 48 hours of injecting this RNA into KAS6/1 myeloma xenografts, high titers of infectious CVA21 virions were detected in the bloodstream. Tumors regressed rapidly thereafter and mice developed signs of myositis. At euthanasia, CVA21 was recovered from regressing tumors and from skeletal muscles. Treatment outcomes were comparable following intratumoral injection of naked RNA or fully infectious CVA21 virus. Dose-response studies showed that an effective oncolytic infection could be established by intratumoral injection of 1μg of infectious RNA. The oncolytic infection could also be initiated by intravenous injection of infectious RNA. Our study demonstrates that INA is a highly promising alternative drug formulation for oncolytic virotherapy.

Original languageEnglish (US)
Pages (from-to)1041-1047
Number of pages7
JournalMolecular Therapy
Volume19
Issue number6
DOIs
StatePublished - 2011

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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