Inovio Pharmaceuticals, Inc., is focused on the discovery, development, and delivery of a new generation of vaccines, called DNA vaccines, to prevent or treat cancers and chronic infectious diseases, reported that its next generation surface skin electroporation technology was successfully used to significantly enhance the delivery of small interfering RNA (siRNA) molecules to skin in animal studies. The data was published in the journal Molecular Therapy - Nucleic Acids in a paper entitled, "Optimized in vivo transfer of small interfering RNA targeting dermal tissue using in vivo surface electroporation."

While Inovio has multiple ongoing human trials demonstrating the efficacy of its electroporation technology to deliver synthetic DNA-based vaccines to both skin and muscle, this is the first time that this technology has been applied to the delivery of siRNA molecules.

Recently, siRNAs have demonstrated their potential as novel therapeutics due to their ability to induce robust, sequence specific gene silencing in cells. Using siRNA to induce RNA interference (RNAi) could become a promising therapeutic approach to treat many currently untreatable disorders, such as some cancers and many viral and genetic diseases. This preclinical study of Inovio's novel delivery method demonstrated positive results using its minimally invasive, low-voltage surface electroporation technology to successfully delivery siRNA to the skin.

The primary point of this study was to establish whether electroporation is able to accomplish effective delivery of RNA in vivo. The successful outcome of this study highlights the far-reaching therapeutic potential for Inovio's electroporation technology. Preclinical and clinical studies have demonstrated that electroporation, as an effective physical delivery method, can improve both the expression and immunogenicity of DNA vaccines by up to 100-fold.

Dr. J. Joseph Kim, president and CEO, said "Perhaps the biggest hurdle in realizing the full potential of RNA-based therapies is the lack of proper and efficient delivery of siRNA molecules. This study supports the idea that Inovio's proprietary electroporation technology can successfully deliver breakthrough RNA therapies with the same efficacy and safety in which we deliver DNA therapies. Most important, our delivery platform could pave the way for the development of targeted RNA-based therapies for diseases and conditions that are now considered untreatable."

Researchers in this study investigated the optimization of electrical parameters for a novel low-voltage electroporation (EP) method to deliver RNA to dermal tissue in vivo. Initially, the electrical parameters were optimized for dermal delivery of plasmid DNA encoding green fluorescent protein (GFP) using this novel surface dermal EP device at as little as 10V voltage parameters. The device was also assessed for the electronic transfer of siRNA into dermal tissue and Inovio researchers observed robust transfection of tagged-siRNA in the skin. The researchers then assessed whether the successful transfer of siRNA led to gene knockdown (silencing) in vivo. Using a reporter gene construct encoding GFP and tagged siRNA targeting the GFP message, researchers demonstrated simultaneous transfection of the siRNA to the skin via EP and the concomitant knockdown of the reporter gene signal. The siRNA delivery was accomplished with no evidence of injection site inflammation or local tissue damage. The minimally invasive low-voltage EP method is able to efficiently deliver functional siRNA molecules to dermal tissue in a tolerable manner.

In our cells, genes produce proteins that determine all body functions. Sometimes these genes produce proteins harmful to the body or cause improper protein accumulation or protein activity. The goal of gene silencing is to reduce or eliminate the production of select proteins that cause or serve the development of diseases at the RNA level. By interfering with protein production, siRNA and RNAi could potentially play a role in controlling or eliminating diseases such as cancers and infections. To achieve this goal, siRNA must be efficiently delivered into cells. Electroporation has a well-established track record of delivering useful drugs and biologics into cells to perform their useful function.

Inovio is revolutionizing vaccines to prevent and treat today's cancers and challenging infectious diseases. Its SynCon vaccines are designed to provide universal cross-strain protection against known as well as newly emergent unmatched strains of pathogens such as influenza.