Intravenous administration of adenoviral vectors results mostly in hepatocyte transduction and subsequent hepatotoxicity. Because hepatocytes express high levels of the primary adenovirus receptor CAR, untargeting hepatocytes requires CAR-binding ablation. The amino acid residues of the viral fiber responsible for CAR-binding are known. We have constructed a mutant adenoviral vector unable to bind CAR and studied vector biodistribution and hepatotoxicity after intravenous administration. In contrast to a vector with wild-type fiber, the infectivity of the CAR-ablated vector is greatly reduced and not susceptible to inhibition with wild-type knob. Biodistribution and hepatotoxicity are, however, not affected by CAR-binding ablation. A possible explanation could be related to an increased blood persistence detected for the CAR-ablated vectors combined with their residual infectivity through other receptors.

Original languageEnglish
Pages (from-to)1347-1353
Number of pages7
JournalGene therapy
Issue number17
StatePublished - 2001


  • Adenovirus
  • Biodistribution
  • CAR
  • Vector


Dive into the research topics of 'CAR-binding ablation does not change biodistribution and toxicity of adenoviral vectors'. Together they form a unique fingerprint.

Cite this