CAR-binding ablation does not change biodistribution and toxicity of adenoviral vectors

R. Alemany, D. T. Curiel

Research output: Contribution to journalArticlepeer-review

234 Scopus citations

Abstract

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
Volume8
Issue number17
DOIs
StatePublished - Sep 22 2001
Externally publishedYes

Keywords

  • Adenovirus
  • Biodistribution
  • CAR
  • Vector

Fingerprint 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