Fibrin scaffold promotes adenoviral gene transfer and controlled vector delivery.
Gene therapy using adenoviral vectors in tissue regeneration is hindered by a short duration of transgene expression. It is hypothesized that a fibrin scaffold will enhance delivery of the adenovirus to a wound site, precluding the need for high repeated doses. It was aimed to analyze whether fibrin could deliver a low single dose of viral vector to a wound site, without compromising transfection efficiency. Fibrin scaffold containing adenovirus encoding beta-galactosidase, fibrin alone, adenovirus alone, and no treatment groups were applied to a rabbit ear ulcer model. beta-Galactosidase transgene expression was measured at 7 and 14 days. Transgene expression was enhanced in the fibrin containing adenovirus group at 7 days. By 14 days, there was low expression and no difference between groups. Stereological methods assessing wound healing aimed to determine whether the adenovirus capsid elicited an unfavorable inflammatory response and whether fibrin's beneficial properties were altered by addition of adenovirus. The fibrin adenovirus group showed a wound-healing response similar to fibrin alone, showing maximum cellularity and angiogenesis at 7 days. By 14 days, cellularity and angiogenesis subsided, and this effect was not inhibited by the presence of adenovirus. Adenovirus alone did not cause an unfavorable inflammatory response. It is concluded the fibrin aids in the delivery of a low-dose viral vector, thereby avoiding a chronic inflammatory response, and allowing superior transfection than viral vector alone. This has wide-ranging implications on the use of viral vectors in tissue engineering.
Breen
Ailish
A
National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Galway, Ireland.
Dockery
Peter
P
O'Brien
Timothy
T
Pandit
Abhay
A
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004058:Diffusion / Q000187:drug effects; D016503:Drug Delivery Systems; D005337:Fibrin / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011817:Rabbits; D013499:Surface Properties / Q000187:drug effects; D054457:Tissue Scaffolds; D019076:Transgenes; D001616:beta-Galactosidase / Q000378:metabolism
D005337:Fibrin; D001616:beta-Galactosidase