Ziphius is at the forefront of developing proprietary self-amplifying RNA technologies, coupled with cutting-edge lipid formulations for efficient delivery. This enables us to advance a diverse pipeline, ranging from prophylactic vaccines for infectious diseases and protein supplementation therapies for rare diseases, to next-generation oncology treatments designed to specifically target and eliminate cancer cells. By leveraging this innovative approach, we are advancing the future of medicine across multiple therapeutic areas.
Self-Amplifying RNA
Self-amplifying RNA (saRNA) or replicon RNA is an advanced, next generation, RNA technology that not only carries the genetic instructions for producing a specific protein, but also encodes a viral RNA replicase, enabling it to replicate itself within the body and increase protein production over time. 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 a high and long protein expression at low doses. The technology thus offers multiple advantages over traditional technologies and non-replicating RNA technologies.
Benefits of saRNA
Low dose
Our saRNA platform has proven to be a powerful tool to develop innovative approaches for a range of therapeutic applications, including prophylactic vaccination, gene supplementation, and other advanced therapies. The platform contributes to high levels of sustained antigen or protein production driving potent immune responses at lower initial doses compared to non-replicating mRNA therapies.
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. Its in vivo half-life and inherent immunogenicity can be regulated through the use of various modifications and delivery methods, allowing for optimized use across different applications, from immunogenic vaccines to protein replacement therapies requiring stable, longer-lasting protein expression.
Prolonged and Robust Immune response
During the self-amplification of saRNA within cells, a double-stranded RNA intermediate is formed, which is recognized by intracellular immune sensors due to its similarity to a natural viral infection. As a result, saRNAs act as powerful activators of the immune system, making them valuable tools for a range of therapeutic applications, including vaccination and oncology. Besides, saRNAs are expected to induce higher amounts of the protein of interest at a much lower dosage and for a longer duration. These characteristics of the platform offer the potential for robust immune responses across various treatment areas.
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.
Lipid NanoParticles
Lipid nanoparticle (LNP)-based delivery is a cutting-edge technology to carry nucleic acids into the cell cytoplasm of specific target organs. LNPs provide an extra layer of protection to RNA molecules from RNase-mediated degradation. LNPs consists of a combination of various lipids with each having specific functions. Overall, the lipid bilayer surrounds an aqueous core, where the RNA is incorporated.
The in-house developed LNP library at Ziphius is specifically designed for saRNA delivery and ensures proper encapsulation, stability, and biodegradability of the LNP-saRNA complex. Furthermore, Ziphius is focused on developing LNPs for a variety of administration routes across different vaccine and therapeutic applications. The platform is being optimized to achieve optimal efficacy in infectious disease vaccines, therapies for rare diseases and oncology.
LNP-mediated delivery of saRNA into the cells and induction of an immune response or protein supplementation is carried out as follows:
- Cellular uptake of the LNP by endocytosis and taken up by endosomes.
- A pH change in endosome causes the LNPs to change structure, releasing the saRNA in cytoplasm.
- The saRNA is amplified by its replication machinery and translated in targeted protein in cytosol.
- The proteins generated can induce a targeted immune response, provide therapeutic protein supplementation for rare diseases or oncology treatments by targeting cancer cells, depending on the application.
