Viruses rely on their surface proteins to engage and enter their host target cells. By grafting those protein ligands onto the extracellular vesicles (EV) surface viral tropism is transferred to the EV, allowing the engineered EVs to interact preferentially with the same cells that are targeted by the virus. The concept of transferring viral tropism, in a process called pseudotyping, is an established approach in virus research and viral-based therapies.
Exopharm’s proprietary EV engineering technologies enable predictable surface ligand modification (EVPSÔ) and ability to enhance specific nucleic acid cargo loading (LOADÔ) into EVs. LOADÔ and EVPSÔ form the basis of Exopharm’s FortrexoÔ platform, the first iteration of which has allowed the rapid development of EV-based drugs for the prevention or treatment of viral diseases. The first product to be developed is Fortrexo CoVÔ, to address the current COVID-19 pandemic.
An advantage of FortrexoÔ is that it does not require prior knowledge of the target cell receptor that facilitates viral entry into the host cells. It is also not affected by mutations in the coat protein which might render an established vaccine ineffective, as the mutated virus will likely target the same receptor.
The RNAi cargo be designed to be completely specific for viral pathogens’ target RNA sequences. The Fortrexo platform can be applied to any virus (or other RNA sequence) by differential and appropriate siRNA design.
Viral sequences quickly become accessible when new viruses emerge, therefore coat proteins can be readily incorporated into the next iteration of Fortrexo. Similarly, the genome sequence can be used to identify targets for RNAi to be used as cargo.
Fortrexo has been conceived to bridge the gap between the identification of new potentially pandemic viral strains and the successful development of effective prophylaxes.