Insert Stability and In Vivo Testing of MicroRNA-Detargeted Oncolytic Picornaviruses

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Although a variety of oncolytic viruses under clinical investigation have proven to be safe, the overall efficacy of oncolytic viruses as monotherapies has been suboptimal. While responses to combination therapies are much more promising, the development of oncolytic virus monotherapies with enhanced potency is imperative. With this initiative comes the need for improved mechanisms of virus targeting to prevent off-target toxicities. MicroRNA-detargeting has emerged as an invaluable tool for preventing unwanted toxicities of oncolytic viruses, particularly for picornaviruses. Here we describe methods to test the genetic stability of microRNA response elements in vitro and to evaluate the detargeting efficiency and therapeutic index of a microRNA-detargeted picornavirus in vivo. Although the methods described herein are specific to picornaviruses, microRNA-detargeting and these assays can be adapted for different classes of oncolytic viruses.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages77-94
Number of pages18
DOIs
StatePublished - Jan 1 2020

Publication series

NameMethods in Molecular Biology
Volume2058
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Genetic stability
  • MicroRNA
  • Oncolytic picornavirus
  • Targeting
  • Virotherapy

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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