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ZiphiusModel saRNA - Self-Amplifying RNA Technology

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Self-amplifying RNA (saRNA) or replicon RNA has the advantage of having self-replicating features, as the saRNA molecule encodes a viral RNA replicase in addition to the sequence of the protein(s) of interest. Upon cytoplasmic delivery of the saRNA molecule, the viral replicase is translated and generates multiple copies of the original saRNA strands. Consequently, a significantly high amount of a shorter subgenomic RNA encoding the protein(s) of interest is produced. This mechanism leads to high protein expression levels at low doses. The technology thus offers multiple advantages over traditional technologies and non-replicating mRNA technologies.

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Low dose

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.

Broad immune response for vaccination

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.

High tolerability and safety profile

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.

High flexibility and manufacturing efficiency

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.