The noninvasive, quantitative, in vivo assessment of adenoviral-mediated gene delivery in skin wound biomaterials.
Because there are few reports using gene delivery in clinically-approved synthetic matrices, we examined the feasibility of using a noninvasive imaging system to study the kinetics of luciferase gene expression when delivered in an adenoviral vector. Using a mouse model of full thickness injury, we quantified the kinetics of gene expression, determined the optimal dose of particle delivery, and established the temporal importance of drug delivery in obtaining optimal gene expression. Specifically, we found that the ideal time to deliver adenovirus to a graft is during the early phase of graft wound closure (days 0-3 post-operatively) for a peak of gene expression to occur 7 days after delivery. Under these conditions, there is a saturating dose of 6 x 10(8) adenoviral particles per graft. In light of these findings, we examined whether the efficacy of delivery could be increased by modulating the composition of the grafts. When a collagen gene-activated matrix (GAM) containing basic fibroblast growth factor (FGF2) was compared to matrix alone, a significant increase in gene expression is observed when identical amounts of vector are delivered (p<0.05). Taken together, these results show how a noninvasive and quantitative assessment of gene expression can be used to optimize gene delivery and that the composition of matrices can dramatically influence gene expression in the wound bed.
Division of Trauma, Burns and Critical Care, Department of Surgery, 200 W. Arbor Dr., University of California-San Diego, San Diego, CA 92103-8236, USA.
Carrie Y
CY
Peterson
Ashkaun
A
Shaterian
Alexandra K
AK
Borboa
Ana M
AM
Gonzalez
Bruce M
BM
Potenza
Raul
R
Coimbra
Brian P
BP
Eliceiri
Andrew
A
Baird
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism*; D005240:Feasibility Studies; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000293:injuries / Q000503:physiopathology*; D014161:Transduction, Genetic; D014945:Wound Healing / Q000235:genetics* / Q000502:physiology
D001672:Biocompatible Materials; D016222:Fibroblast Growth Factor 2; D008156:Luciferases