Seattle Genova operates a state-of-the-art mRNA/saRNA production facility. As the leading supplier of mRNA/saRNA, our unparalleled experience, technical expertise, and scalability make us an ideal partner for your research projects. Our production processes are fully customizable and scalable to support your needs for discovery and preclinical projects.
The main difference between mRNA and self-amplifying RNA is that saRNA is a much larger molecule as it encodes four extra proteins in addition to the antigen or gene of interest. The four extra proteins are the non-structural proteins, usually derived from an alphavirus, that encode a replicase. This replicase enables amplification of the original strand of RNA upon delivery into the cell, which yields a much higher amount of protein expression and thus a minimal dose of RNA required. However, this also means that saRNA (~10,000 nt) is typically much larger than mRNA (~2,000 nt), and thus more difficult to deliver.
A brief description of the mechanism of this saRNA is as follows: it enters the cytoplasm of the host cell, translates the replicase, which makes a complementary negative copy of the mRNA. This long mRNA strand becomes the template used by Rep to synthesize more saRNA. At the same time, the replicase also binds to a subgenomic promoter in the negative strand to synthesize subgenomic mRNA at ten times greater concentration than genomic RNA, encoding the viral antigen. Since saRNA is already more immunogenic than other RNA molecules, activating several Toll-like receptors, for instance, this elevated expression of viral antigen in vivo causes extremely robust immune responses.
Benefits of self-amplifying RNA
Fast to synthesize
Production is cell-free, does not require a dedicated facility
saRNA immunogens often produce a higher immune response from a smaller dose when compared to mRNA-based immunogens
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