Controlling gene expression in primary cultured cells, such as human keratinocytes is difficult due to the stratum corneum, which ranges from 10-50 urn in thickness and serves as a barrier to the intracellular environment. Methods to introduce gene regulation agents such as oligonucleotides have met with limited success, as both the penetration depth and effectiveness of the regulation strategies vary. The proposed work will develop oligonucleotide-nanoparticle antisense agents as methods for controlling gene expression in keratinocytes. This work will take advantage of newly discovered conjugate properties of the nano-materials including enhanced stability, high penetration ability, and non-toxicity. The ability of these agent to work on genes of relevence in skin biology models will be tested.
The creation of stable methods for the introduction and use of oligonucletdies as gene regulation agents is highly significant, as creating much more effective gene regulation agents often require modifications which are at the cost of a loss of activity or through cellular toxicity. Using nanoparticle agents to deliver and protect nucleic acids is a development that is of great interest for future clinical applicaiton.
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