This application proposes to explore a novel DNA delivery platform for skin that utilizes a stream of ions generated in plasma (charged gas stream) to facilitate the uptake of DNA. This new physical DNA delivery technology differs from other technologies in that it does not utilize chemical or biological agents. It also differs from other physical DNA delivery methods in that it does not require contact between any devices and the skin;therefore, it is noninvasive. Preliminary studies have shown that it is possible to deliver foreign molecules to cells in vitro and plasmid DNA to normal mouse skin in vivo without the adverse stimulation noted when other electrical methodologies are used. Based on these findings, the hypothesis of this proposal is that streamed ion deposition can be used for efficient DNA delivery to skin. This hypothesis will be tested by performing specific aims that characterize its capacity to deliver plasmids encoding reporter molecules. It will also be tested with respect to delivering plasmid encoding an antigen and a secreted protein to explore the methods capacity for prophylactic and therapeutic use.
This study is relevant to public health as the results may lead to treatments for many types of diseases that require the secretion of a therapeutic protein into the blood. In addition, it may lead to a better means of applying DNA vaccines against infectious diseases.
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|Connolly, Richard J; Chapman, Taryn; Hoff, Andrew M et al. (2012) Non-contact helium-based plasma for delivery of DNA vaccines. Enhancement of humoral and cellular immune responses. Hum Vaccin Immunother 8:1729-33|
|Shah, Kevin; Connolly, Richard J; Chapman, Taryn et al. (2012) Electrogenetherapy of B16.F10 murine melanoma tumors with an interleukin-28 expressing DNA plasmid. Hum Vaccin Immunother 8:1722-8|
|Connolly, Richard J; Rey, Jose I; Lambert, Vance M et al. (2011) Enhancement of antigen specific humoral immune responses after delivery of a DNA plasmid based vaccine through a contact-independent helium plasma. Vaccine 29:6781-4|
|Connolly, Richard J; Lopez, Gabriel A; Hoff, Andrew M et al. (2010) Characterization of plasma mediated molecular delivery to cells in vitro. Int J Pharm 389:53-7|
|Connolly, Richard J; Lopez, Gabriel A; Hoff, Andrew M et al. (2009) Plasma facilitated delivery of DNA to skin. Biotechnol Bioeng 104:1034-40|