ISSN:
1524-475X
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
Biocompatible matrices, such as bovine collagen, have demonstrated usefulness in delivering gene therapy vectors that express growth factors to local environments for tissue repair. Unlike animal derived matrices, we have developed a new synthetic matrix consisting of a linear cyclodextrin-polyethyleneglycol co-polymer that is non-covalently cross-linked with di-adamantane-polyethyleneglycol via inclusion complex formation between adamantane and cyclodextrin (CD-Ada). We performed both in vitro and in vivo experiments for biocompatibility and localized transgene expression using a recombinant adenovirus (rAd) vector containing either the reporter gene, GFP, or the therapeutic gene, PDGF-B. In vitro results demonstrated cell migration, adenoviral transduction, and gene expression with no visible signs of toxicity in human skin fibroblasts. Qualitative gene expression from the CD-Ada containing rAd was delayed by approximately two days when compared to collagen, but the level of expression was greater over a longer period of time. In vivo experiments demonstrated gene expression after local delivery to mouse skin using rAd-GFP in CD-Ada. Again, the expression was slightly delayed but duration of expression was comparable to collagen. Expression studies using rAd-PDGF-B, were performed in the rat polyvinyl alcohol sponge model and showed comparable quantitative DNA and RNA levels between CD-Ada and collagen (DNA: 4.1 × 1010 and 4.5 × 1010 MEQ of PDGF-B/assayed sponge, respectively; RNA: 7.0 × 108 and 3.2 × 108 MEQ of PDGF-B/assayed sponge, respectively). Additionally, we explored the use of plasmid DNA with the CD-Ada matrix and observed PDGF-B expression in vivo. Our results show that this new delivery system provides a safe, efficient, and adaptable medium for both viral and non-viral gene delivery.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1067-1927.2004.0abstractf.x
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