Our Technology

Ziphius Vaccines is developing proprietary self-amplifying mRNA technologies combined with innovative lipid formulations for targeted delivery. This allows us to generate a broad pipeline of late pre-clinical and early clinical stage products, including prophylactic vaccines against infectious diseases and gene supplementation therapies for the treatment of rare genetic disorders.


DNA is the source code of life, it stores the instructions for protein synthesis. Proteins itself are the workhorses of our cells and carry out all crucial functions necessary for human life. To create proteins, our DNA is transcribed in messenger RNA (mRNA) which transports the information encoded in the nucleus' DNA to the cytoplasm, where the ribosomes convert it into proteins.

mRNA-based vaccines use an mRNA sequence that codes for a disease-specific protein (antigen). This sequence is translated by the human body into the corresponding antigen and is displayed on the cell surface where it is recognized by the immune system, preparing it to fight the real thing.

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Self-Amplifying RNA

Messenger RNA

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.

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Self-Amplifying RNA

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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Benefits of saRNA

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.

Lipid NanoParticles


Lipid nanoparticle (LNP)-based delivery is a cutting-edge technology to carry nucleic acids into the cell cytoplasm of specifictarget 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 also focused on making LNPs for various administration routes for vaccination and supplementation therapies. The platform is being optimized to target specific organs and tissues, to minimize acute and chronic toxicity, and to acquire the most optimal prophylactic vaccination or gene supplementation effect.

LNP-mediated delivery of saRNA into the cells and induction of an immune response or gene supplementation is carried out as follows:

  1. Cellular uptake of the LNP by endocytosis and taken up by endosomes.
  2. A pH change in endosome causes the LNPs to change structure, releasing the saRNA in cytoplasm.
  3. The saRNA is amplified by its replication machinery and translated in targeted protein in cytosol.
  4. The proteins can induce a targeted immune response for vaccination or act as a protein supplementation therapy.