Applications of self-replicating RNA.

Self-replicating RNA viral vectors have been engineered for both prophylactic and therapeutic applications. Mainly the areas of infectious diseases and cancer have been targeted. Both positive and negative strand RNA viruses have been utilized including alphaviruses, flaviviruses, measles viruses and rhabdoviruses. The high-level of RNA amplification has provided efficient expression of viral surface proteins and tumor antigens. Immunization studies in animal models have elicit robust neutralizing antibody responses. In the context of infectious diseases, immunization with self-replicating RNA viral vectors has provided protection against challenges with lethal doses of pathogens in animal models. Similarly, immunization with vectors expressing tumor antigens has resulted in tumor regression and eradication and protection against tumor challenges in animal models. The transient nature and non-integration of viral RNA into the host genome are ideal features for vaccine development. Moreover, self-replicating RNA viral vectors show great flexibility as they can be applied as recombinant viral particles, RNA replicons or DNA replicon plasmids. Several clinical trials have been conducted especially in the area of cancer immunotherapy.