The inherent limitations of bolus gene delivery may be avoided by surface immobilization of DNA onto biomaterial scaffolds.  As an alternative to current immobilization approaches, we chemically bind plasmid DNA to a substrate via an enzymatically-labile peptide sequence, allowing for cell-responsive gene delivery.  In our design, the DNA is functionalized using a peptide nucleic acid (PNA) clamp. Coupling peptides, including a matrix metalloproteinase-1 (MMP-1) degradable sequence, are attached to this conjugate to form DNA-PNA-peptide (DPP) conjugates. In this work, we demonstrate DPP formation and immobilization to a model gold surface. Transfection studies were completed with NIH/3T3 cells and the functionalized substrates to demonstrate MMP-1-responsive release of DNA from the surfaces. Currently, we are exploring the tunability of the system by decreasing the number of tethers between the DNA and the surface.  We are also transitioning this immobilization system to another substrate to explore the broader applicability of the delivery mechanism.

Surface immobilization of plasmid DNA with a cell-responsive tether for substrate-mediated gene delivery

239th National Meeting (2010)

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