An adenovirus vector with a chimeric fiber incorporating stabilized single chain antibody achieves targeted gene delivery

S. J. Hedley, A. Auf der Maur, S. Hohn, D. Escher, A. Barberis, J. N. Glasgow, J. T. Douglas, N. Korokhov, D. T. Curiel

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Adenovirus (Ad) vectors are of utility for many therapeutic applications. Strategies have been developed to alter adenoviral tropism to achieve a cell-specific gene delivery capacity employing fiber modifications allowing genetic incorporation of targeting motifs. In this regard, single chain antibodies (scFv) represent potentially useful agents to achieve targeted gene transfer. However, the distinct biosynthetic pathways that scFv and Ad capsid proteins are normally routed through have thus far been problematic with respect to scFv incorporation into the Ad capsid. Utilization of stable scFv, which also maintain correct folding and thus functionality under intracellular reducing conditions, could overcome this restriction. We genetically incorporated a stable scFv into a de-knobbed, fibritin-foldon trimerized Ad fiber and demonstrated selective targeting to the cognate epitope expressed on the membrane surface of cells. We have shown that the scFv employed in this study retains functionality and that stabilizing the targeting molecule, per se, is critical to allow retention of antigen recognition in the adenovirus capsid-incorporated context.

Original languageEnglish
Pages (from-to)88-94
Number of pages7
JournalGene therapy
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

Keywords

  • Adenovirus
  • Stable scFv
  • Targeting

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    Hedley, S. J., Auf der Maur, A., Hohn, S., Escher, D., Barberis, A., Glasgow, J. N., Douglas, J. T., Korokhov, N., & Curiel, D. T. (2006). An adenovirus vector with a chimeric fiber incorporating stabilized single chain antibody achieves targeted gene delivery. Gene therapy, 13(1), 88-94. https://doi.org/10.1038/sj.gt.3302603