Improved systemic antitumor therapy with oncolytic adenoviruses by replacing the fiber shaft HSG-binding domain with RGD

Gene Ther. 2012 Apr;19(4):453-7. doi: 10.1038/gt.2011.106. Epub 2011 Jul 21.


Retargeting oncolytic adenoviruses from their systemic preeminent liver tropism to disseminated tumor foci would highly improve the efficacy of these agents at eradicating tumors. We have replaced the KKTK fiber shaft heparan sulfate glycosaminoglycan-binding domain with an RGDK motif in order to achieve simultaneously liver detargeting and tumor targeting. When inserted into a wild-type backbone, this mutation palliated liver transaminase elevation and hematological alterations in mice. Importantly, when tested in a backbone that redirects E1A transcription towards pRB pathway deregulation, RGD at this novel shaft location also improved significantly systemic antitumor therapy compared with the broadly used RGD location at the HI-loop of the fiber knob domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Binding Sites
  • Cell Line, Tumor
  • Gene Transfer Techniques
  • Genetic Vectors
  • Heparitin Sulfate / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / therapy*
  • Oligopeptides*
  • Oncolytic Virotherapy / methods*
  • Receptors, Cell Surface / metabolism


  • Oligopeptides
  • Receptors, Cell Surface
  • glycosaminoglycan receptor
  • arginyl-glycyl-aspartic acid
  • Heparitin Sulfate