title: 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.
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.
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Emily R
authors.initials: ER
authors.lastname: McFall
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6.
authors.forename: Lyndsay M
authors.initials: LM
authors.lastname: Murray
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: John A
authors.initials: JA
authors.lastname: Lunde
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada; University of Ottawa Centre for Neuromuscular Disease, Ottawa, Ontario, Canada.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Jasmin
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada; University of Ottawa Centre for Neuromuscular Disease, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kothary
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; University of Ottawa Centre for Neuromuscular Disease, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: rparks@ohri.ca.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Parks
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism / Q000821:virology; D018482:Muscle, Skeletal / Q000821:virology*; D011991:Receptors, Virus; D019076:Transgenes; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; D011991:Receptors, Virus; D014764:Viral Proteins
keywords: Adenovirus; Muscle; Transduction; Viral vector