A reduction in the human adenovirus virion size through use of a shortened fibre protein does not enhance muscle transduction following systemic or localised delivery in mice

Emily R. McFall, Lyndsay M. Murray, John A. Lunde, Bernard J. Jasmin, Rashmi Kothary, Robin J. Parks*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We have investigated whether reducing the overall size of adenovirus (Ad), through use of a vector containing a shortened fibre, leads to enhanced distribution and dissemination of the vector. Intravenous or intraperitoneal injection of Ad5SlacZ (12 nm fibre versus the normal Ad5 37 nm fibre) or Ad5SpKlacZ (shortened fibre with polylysine motif in the H-I loop of fibre knob domain) led to similar levels of lacZ expression compared to Ad5LlacZ (native Ad5 fibre) in the liver of treated animals, but did not enhance extravasation into the tibialis anterior muscle. Direct injection of the short-fibre vectors into the tibialis anterior muscle did not result in enhanced spread of the vector through muscle tissue, and led to only sporadic transgene expression in the spinal cord, suggesting that modifying the fibre length or redirecting viral infection to a more common cell surface receptor does not enhance motor neuron uptake or retrograde transport. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Original languageEnglish
Pages (from-to)444-453
Number of pages10
JournalVirology
Volume468
DOIs
Publication statusPublished - Nov 2014

Keywords

  • Adenovirus
  • Transduction
  • Viral vector
  • Muscle
  • MEDIATED GENE-TRANSFER
  • CENTRAL-NERVOUS-SYSTEM
  • COXSACKIE B VIRUSES
  • IN-VIVO
  • CHROMOSOMAL INTEGRATION
  • TRANSGENE EXPRESSION
  • RETROGRADE TRANSPORT
  • NONHUMAN-PRIMATES
  • VECTORS
  • RECEPTOR

Fingerprint

Dive into the research topics of 'A reduction in the human adenovirus virion size through use of a shortened fibre protein does not enhance muscle transduction following systemic or localised delivery in mice'. Together they form a unique fingerprint.

Cite this