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Ziphius - Model mRNA - Self-Amplifying RNA Technology
Proteins are large biological macromolecules that are essential parts of organisms and participate in virtually every process within cells. Proteins are created through the process of gene expression, in which genetic information from DNA is transcribed into messenger RNA (mRNA) in the cell nucleus. Next, the mRNA gets translated by ribosome in the cytoplasm into functional proteins. RNAs are long polymeric nucleic acid molecules composed of four different building bases, the so-called nucleotides. Although RNA is transcribed with only four bases, these can be linked in unique orders and modified in numerous ways as the RNAs mature. Hence, RNA has the capacity to encode an extensive variety of protein(s) of interest, and hence can be used as vehicles to transfer a broad spectrum of disease-specific antigens for prophylactic vaccination against many infectious disease or proteins via gene supplementation therapies for rare genetic disorders.
Our saRNA platform has demonstrated to be a powerful tool for prophylactic vaccination against infectious diseases, as it ensures high levels of sustained antigen production that are able to drive equivalent or more potent immune responses at lower initial doses compared to those achieved by non-replicating mRNA vaccines. Similarly, the platform provides the possibility of transferring large, yet transient, amounts of proper proteins or polypeptides lacking in patients with rare genetic disorders.
During self-amplification of the saRNA inside the cell, a double-stranded RNA intermediate is generated, which is recognized by intracellular immune sensors as it mimics a natural viral infection. Hence, saRNAs are potent activators of the immune system, making them ideal tools for vaccination. In addition, we optimized our platform to be able to combine multiple RNA sequences, leading to a broad immune protection consisting of neutralizing antibody responses to prevent pathogenic entry and cell-mediated immunity to attenuate infectious breakthrough and disease severity.
Unlike DNA, RNA does not have to enter the nucleus to be effective. To be specific, our saRNA is a non-infectious and non-integrating molecule and thus causes no potential risk of infection or incorporation in the host genome. Additionally, RNA is easily and relatively rapidly degraded by normal cellular processes, making it a transient and safe technology. In addition, both its in vivo half-life and inherent immunogenicity can be regulated through the use of various modifications and delivery methods, depending on its envisioned application (i.e. prophylactic vaccination which requires some immunogenicity versus gene supplementation therapy which needs longer and stable expression). Altogether, this further increases the safety profile.
Our saRNA platform is flexible and rapidly scalable, allowing Ziphius to quickly respond to new medical needs, such as rapidly emerging infectious outbreaks. Only minor changes are necessary to develop a new saRNA construct and this enables Ziphius to constantly provide in-time and cost-effective solutions.