Article

A matrix reservoir for improved control of non-viral gene delivery. J Control Release

Network of Excellence in Functional Biomaterials, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.
Journal of Controlled Release (Impact Factor: 7.71). 03/2009; 136(3):220-5. DOI: 10.1016/j.jconrel.2009.02.006
Source: PubMed

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.

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    • "Other studies have also explored the use of nonviral delivery of siRNA, microRNAs, and shRNAs through polycation, liposomal, and biochemical chaperoning [5]. Specifically, these studies used a variety of platforms to deliver the siRNA or shRNA and ranged from hydrogels [30]–[34] films [35], [36], nanoparticles [37]–[39], sponges [40]–[41], and even creams [42]. Collectively, these studies targeted various genes that play a role in a variety of biological processes. "
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    Full-text · Article · Dec 2012 · PLoS ONE
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    • "Such prolonged and enhanced transfection efficiency by scaffolds is likely due to the sustained release and localized concentration of siRNA to cells. Similar findings were also observed previously [53] [54]. The coencapsulation of siCOL1A1 and CADY within PCLEEP fibers resulted in similar COL1A1 knockdown as compared to siCOL1A1/TKO complexes. "
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    • "A 0.3w/v% type I atelocollagen solution was freeze-dried and crosslinked with 1- ethyl-3-[3-dimethylaminopropyl]carbodiimide and N-hydroxysuccinimide (EDC/ NHS) to make the collagen scaffolds, as described elsewhere [24]. Interleukin-10 plasmid-dendrimer polyplexes (pIL-10) were prepared by incubating IL-10 plasmids with SuperFectÔ. 2 mg of plasmid complexed to 30 mg of dendrimer was added to each scaffold and the IL-10 polyplexes (pIL-10) were allowed to adsorb for 3 h. "
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