The Segura Laboratory is exploring non-viral gene delivery from scaffolds as an alternative approach to protein delivery. Although protein delivery has been widely explored to promote vascularization and tissue repair, the delivery of native proteins requires supra-physiological doses of protein to reach therapeutic levels, often raising safety concerns. In the gene delivery approach, a plasmid DNA, minicircle DNA, or mRNA that encodes for a desired therapeutic protein (e.g. growth factor, receptor, transcription factor) is loaded within the scaffold. Upon implantation, the scaffold is infiltrated with cells. Some of the cells become transfected with the transgene and begin expressing the therapeutic protein. These proteins will either act on the cells that express them (autocrine signaling) or on neighboring cells (paracrine signaling). The limitation of this approach has been the inability to attain sufficient levels of transgene expression to observe therapeutic benefits.
Over the past decade, our laboratory has worked to design scaffolds that can effectively deliver genes. Through this work we have engineered a variety of DNA loaded hydrogel scaffolds capable of achieving gene transfer in vivo. We are currently working to develop DNA loaded injectable materials that can restore blood supply to ischemic tissues.