A matrix reservoir for improved control of non-viral gene delivery.
ABSTRACT Non-viral gene delivery suffers from a number of limitations including short transgene expression times and low transfection efficiency. Collagen scaffolds have previously been investigated as in vitro DNA reservoirs, which allow sustained release of genetic information. Efficient viral gene-transfer from these scaffolds has previously been demonstrated. However, due to concerns about the safety of viral gene therapy, the use of non-viral vectors may be preferable. In this study a DNA-dendrimer complex embedded in a cross-linked collagen scaffold was investigated as a reservoir for non-viral delivery. Elution from the scaffolds and transfection of seeded rat mesenchymal stem cells were used to evaluate the scaffold's ability to act as a reservoir for the complexes. Elution from the scaffolds was minimal after 2 days with a total of 25% of the complexes released after 7 days. Extended transgene expression after DNA-dendrimer complex delivery from the scaffolds in comparison to direct delivery to cells was observed. The elongated transfection period and relatively high levels of reporter gene expression are significant advantages over other non-viral gene therapy techniques. This platform has the potential to be an effective method of scaffold-mediated gene delivery suitable for in vitro and in vivo applications.
- SourceAvailable from: Saman NazarianJournal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2011; 57(14).
- Journal of the Saudi Heart Association 01/2011; 23(3):182-182.
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ABSTRACT: The increasing knowledge about the roles of different genes involved in both acquired and hereditary diseases has made gene delivery an ever promising weapon in disease treatments. Different gene delivery strategies have been investigated in the past three decades among which non-viral gene delivery has received increasing attention due to a number of evident benefits. Delivery of a therapeutic gene to the targeted site in non-viral gene delivery is often aided by vectors such as polymers, lipids, peptides and nanoparticles, but their efficiencies and side effects such as cytotoxicity have stimulated extensive studies to explore how these effects can be balanced at the molecular-cell levels. Successful treatment strategies will ideally work on the basis of high transfection efficiency, low cell toxicity and the minimisation of other possible side effects. The vectors must overcome a number of physical and biological barriers after systemic or local administration. This review focuses on the molecular biophysics underlying non-viral gene delivery using different molecular vectors. A number of representative scientific studies will be introduced to demonstrate the relationships between the physicochemical properties of the DNA/vector complexes and their transfection efficiencies.Annual Reports Section C"" (Physical Chemistry)""" 06/2010; 106.