Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

The noninvasive, quantitative, in vivo assessment of adenoviral-mediated gene delivery in skin wound biomaterials. Biomaterials 2009 Dec;30(35):6788-93

Date

09/29/2009

Pubmed ID

19781761

Pubmed Central ID

PMC2948440

DOI

10.1016/j.biomaterials.2009.07.069

Scopus ID

2-s2.0-70349847557   10 Citations

Abstract

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.

Author List

Peterson CY, Shaterian A, Borboa AK, Gonzalez AM, Potenza BM, Coimbra R, Eliceiri BP, Baird A

Author

Carrie Peterson MD, MS, FACS, FASCRS Associate Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenoviridae
Animals
Biocompatible Materials
Feasibility Studies
Fibroblast Growth Factor 2
Gene Transfer Techniques
Genes, Reporter
Genetic Vectors
Kinetics
Luciferases
Male
Mice
Mice, Inbred C57BL
Skin
Transduction, Genetic
Wound Healing