Protein therapy with self-amplifying RNA (saRNA) allows the production of a therapeutic protein in cells for longer and at lower doses than standard mRNA. SaRNA contains the genetic information for a replicase that amplifies its own RNA, resulting in stronger and more sustained protein expression. Compared to linear mRNA, saRNA requires less RNA to achieve a comparable or higher effect, for example, detection of luciferase in mice took up to 3 weeks versus 1 week. In CAR T cell therapy, saRNA prolongs CAR expression, improves tumor suppression in an acute lymphoblastic leukemia model, and enables co-expression of multiple proteins for OR and AND logic gates. SaRNA is used in oncology to encode antigens or cytokines, in metabolic diseases for long-term expression of proteins without integration into the genome. Production begins with plasmid DNA as a template for in vitro transcription, which promotes scalability. These properties make saRNA a more effective platform for protein therapies with better safety and availability.[1][2][3]