Selfamplifying

Self-amplifying describes systems or molecules that increase their own quantity or activity without external input. In biology and biotechnology, the term is often applied to self-amplifying RNA (saRNA), a class of RNA that encodes a replicase enzyme enabling intracellular replication of the RNA.

This replication leads to amplified production of the encoded protein, such as an antigen, within the host cell. saRNA is typically derived from alphaviruses and is designed so that replication amplifies only the RNA and protein of interest, ideally limiting the release of infectious material.

In vaccines, saRNA can produce strong antigen expression at lower doses compared with conventional non-replicating mRNA, offering potential dose-sparing advantages. This has driven research into saRNA vaccines and therapies, with several preclinical and clinical studies exploring safety, immunogenicity, and manufacturability. Challenges include ensuring controlled replication, minimizing potential safety risks, and addressing manufacturing and stability considerations.

Beyond vaccines, self-amplifying circuits appear in synthetic biology, where genetic constructs are designed to boost signal output or maintain expression levels through positive feedback or replicative elements. In virology and molecular biology, natural self-amplifying processes occur when replicative enzymes enable rapid amplification of viral or host RNA, influencing disease dynamics and host responses.

The term is sometimes used more loosely to describe any component that increases its own activity or abundance through feedback loops. See also replicon RNA, alphavirus replicase, mRNA vaccine.