Gene Compensation by Non-Viral Gene Therapy: Concepts and Vision

Eukarÿs’ paradigm: safe, efficient, well-tolerated, economically viable, synthetic non-viral gene therapy for monogenic and complex multifactorial disorders.

The synthetic gene therapy developed by Eukarÿs relies on uses of double-stranded DNA molecules, which are produced artificially. This synthetic DNA contains both the C3P3 gene, plus one or several target genes under control of the enzyme. Once the C3P3 enzyme is expressed in the targeted organ, the enzyme self amplifies in the cytoplasm, and then transcribes the genes of interest and generates mature mRNA molecules.

Synthetic gene therapy sharply differs from any other existing gene therapy approaches:

• Efficacy: Eukarÿs’ synthetic gene therapy relies on the use of the artificial C3P3 expression technology, which generates large amounts of target mRNA(s). Our therapeutic approach therefore radically differs from the standard non-viral gene therapy, which has limited efficacy due to the poor mRNA amounts associated to this latter.
• Safety: our synthetic gene therapy approach has be designed to prevent insertional mutagenesis of the artificial double-stranded DNA in the host-cell genome. Such genetic recombination leads to major safety issues due to the risk of developping solid or hematologic cancers. Eukarÿs synthetic gene therapy therefore radically differs from viral gene therapy, whose uses is limited to ultra-severe diseases because of such risk.
• No size limitations: any gene can be expressed by synthetic gene therapy, with no limitation in length of genes. Our therapeutic approach therefore radically differs from viral gene therapy, which is limited by the packaging capacity of viral vectors, in particular AAV vectors. Moreover, our synthetic gene therapy approach makes it possible to express and/or inhibit several genes at the same time under control of the C3P3 enzyme. This feature allows the development of treatments for rare simple monogenic diseases, as well as common complex multifactorial disorders requiring multiple gene targeting.