On 18 July 2013 Inovio announced that the use of its proprietary electroporation technology significantly enhanced the ability of a DNA therapy to stimulate blood vessel growth, which may be beneficial for the treatment of critical limb ischaemia and other forms of peripheral arterial disease.
Critical limb ischaemia markedly reduces blood flow, resulting in notable medical impacts and death. In a mouse model, delivery of a synthetically optimised hypoxia-inducible factor-1 alpha (HIF-1a) gene using Inovio’s Cellectra electroporation delivery technology produced significant growth of new blood vessels and improved limb blood flow, limb function recovery, and survival from limb necrosis and amputation. The results were published in a paper entitled, “In vivo electroporation of constitutively expressed HIF-1a plasmid DNA improves neovascularization in a mouse model of limb ischemia,” in the Journal of Vascular Surgery.
J Joseph Kim, Inovio’s president and CEO, said: “We have tremendous momentum 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 peripheral arterial disease using angiogenic growth factor DNA therapies without success. This study shows that combining our synthetic gene optimisation techniques with our proprietary delivery systems could lead to an effective therapy. While early, this new application in treating peripheral arterial disease and other major chronic diseases offers Inovio a promising therapeutic avenue”.
In the study, the gene sequence for HIF-1a was synthetically optimised 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. One group received HIF-1a DNA delivered with electroporation (n=13), one group received HIF-1a DNA without electroporation (n=14) and (3) one group received a control empty plasmid (pVAX) delivered with electroporation (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 electroporation delivery of synthetically optimised HIF-1a plasmid DNA significantly improved blood flow in the left hind legs and reduced necrosis in a mouse model of hind limb ischaemia 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.