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.
journal_name
Gene Therjournal_title
Gene therapyauthors
Hedley SJ,Auf der Maur A,Hohn S,Escher D,Barberis A,Glasgow JN,Douglas JT,Korokhov N,Curiel DTdoi
10.1038/sj.gt.3302603subject
Has Abstractpub_date
2006-01-01 00:00:00pages
88-94issue
1eissn
0969-7128issn
1476-5462pii
3302603journal_volume
13pub_type
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