Naked DNA-Mediated Gene Therapy: Clinical Application of Tissue Inhibitors of Matrix Metalloproteinase

摘要

After all, once the first phase of Human Genome Project (sequence) are finished, the obvious questions become what are the functional relevances of these proteins and how to deliver these functional proteins. While the functional relevance of the protein is a very important aspect of the Proteomics, developing of a new delivery platform for administration of functional proteins faces even bigger challenge. Recombinant protein held out the promise of therapeutics based on biology rather than chemis ry. However, the cost-effective manufacturing of active pro ems at large scale has been a technical hurdle and the sho t half-life of many proteins in the blood has been a bigger bio ogical hurdle to the widespread development of therapeutic proteins. Gene therapy aimed on gene delivery into living tissues has significant implications in various clinical applications. Although the current virus-mediated gene delivery is the major route for gene therapy, it faces a limitati )n due to the serious side effects. Among the nonviral techniques for gene transfer in vivo, the direct injection of plasmid DNA has been widely explored. Tissue inhibitor of metalloproteinase (TIMP) is a secreted protein, which specifically inhibit matrix metalloproteinase (MMP). Overexpression of MMP has been linked to many diseases such as cancer, cardiovascular restenosis, arthritis, and inflammatory diseases. Systemic delivery TIMP gene by a single inteamuscular injection of TIMP DNA will be dscussed in the animal models of cancer and arthritis.