Insertion of an RGD motif into the HI loop of adenovirus fiber protein alters the distribution of transgene expression of the systemically administered vector.
Adenoviral vectors are attractive gene delivery vehicles, but their in vivo utility is reduced by lack of cell-specific infection. Tropism modification of the virion by genetic manipulation of capsid proteins is an attractive strategy to achieve targeted transduction. However, no genetic targeting strategies have yet been shown to modify the distribution of transgene expression following systemic administration of vector. This is an essential requirement if such approaches are to form a basis for further vector develop- ment. In this report we present data showing that insertion of a RGD motif into the HI loop of the adenoviral fiber knob results in a significant change in transgene expression profile following intravenous administration. The key finding that a motif in the HI loop is available for cellular interaction when administered systemically means that such modifications can be rationally considered as a foundation upon which further genetic modifications can be superimposed for targeted systemic gene therapy.
Reynolds
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P
Gene Therapy Center, University of Alabama at Birmingham, 1824 Sixth Avenue South, Room WTI 620, Birmingham, Alabama 35294-3300, USA.
Dmitriev
I
I
Curiel
D
D
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015870:Gene Expression; D018390:Gene Targeting; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D008810:Mice, Inbred C57BL; D019076:Transgenes