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Synthetically Optimized HIF-1 Alpha DNA Delivered with Inovio's Electroporation Technology Provides Significant Therapeutic Effects for Peripheral Arterial Disease in Animal Model
Date:7/18/2013

omentum and clinical data in achieving best-in-class immune responses with our SynCon® DNA vaccines delivered using our CELLECTRA electroporation system. Others have attempted to treat PAD using angiogenic growth factor DNA therapies without success. This study shows that combining our synthetic gene optimization techniques with our proprietary delivery systems could lead to an effective therapy. While early, this new application in treating PAD and other major chronic diseases offers Inovio a promising therapeutic avenue and additional commercial opportunity."

In this study, the gene sequence for HIF-1α was synthetically optimized to enhance expression of the growth factor. This DNA therapy was then delivered using Inovio's CELLECTRA constant current electroporation device, which has been shown to enhance the delivery of DNA plasmids by a 1000 fold using a millisecond pulse. A total of 39 mice were divided into 3 groups: (1) one group receiving HIF-1α DNA delivered with electroporation (EP) (n=13); (2) one group receiving HIF-1α DNA without EP (n=14) and (3) one group receiving a control empty plasmid (pVAX) delivered with EP (n=12). The left femoral artery in each mouse was tied up surgically to simulate an arterial blockage. The right legs were not treated and served as internal controls. The mice were then observed and scored for their limb function. Blood flow in their legs was measured by laser Doppler perfusion imaging.

The results demonstrated that EP delivery of synthetically optimized HIF-1α plasmid DNA significantly improved blood flow in the left hind legs and reduced necrosis (premature cell death) in a mouse model of hind limb ischemia when compared to the results from the two control groups. The treatment also improved survival from severe limb damage and amputation, reduced tissue damage, and increased the number of new capillaries and formation of larger collateral vessels.

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SOURCE Inovio Pharmaceuticals, Inc.
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