The discovery of mRNA technology as a suitable platform for vaccines was a breakthrough in contemporary medicine. Scientists for decades had researched messenger RNA as a means to use human cells to make proteins that could induce immune responses. Though the idea was scientifically appealing, technical barriers like delivery mechanisms, stability, and scalable manufacturing kept mRNA treatments mostly in the laboratory. The pandemic of COVID-19, though, pushed for quick innovation. Organizations globally rallied to come up with vaccines through various technologies. Some of them chose to invest in a less traditional method called self-amplifying mRNA, or sa-mRNA.
Self-amplifying mRNA is a type of mRNA that contains genetic information not just to create the target antigen but also to replicate itself within the cell. This self-replication mechanism enables reduced dosing with the ability to generate a robust immune response. The probable advantages are sustained antigen expression and enhanced vaccine stability. As major pharmaceutical companies developed traditional mRNA vaccines, a smaller cohort of companies focused on optimizing the self-amplifying platform.
One of the firms that made this commitment was San Diego, California-based Arcturus Therapeutics. Founded by Joseph E. Payne in 2013, Arcturus built upon two proprietary technologies that were the basis of its mRNA vaccine programs: the LUNAR® lipid nanoparticle delivery system and the STARR® self-amplifying mRNA platform. These products were engineered to be used together, delivering RNA effectively into human cells while also maintaining robust antigen expression over a long period. When COVID-19 broke out as a global pandemic in early 2020, Arcturus was well-suited with an internal organization to shift toward pandemic vaccine development.
Arcturus began development of its COVID-19 vaccine candidate during the first half of 2020. In contrast to the Moderna and Pfizer-BioNTech vaccines, both of which utilized traditional mRNA with relatively high dosages, Arcturus turned its attention to sa-mRNA to hopefully provide comparable efficacy with less material per dose. The bonus was that it also minimized manufacturing burdens, which became especially crucial as nations worldwide experienced supply shortfalls and distribution bottlenecks.
The resulting vaccine, subsequently named KOSTAIVE®, moved through clinical trials and regulatory approval within a highly competitive and expedited timeline. In 2024, Japan’s Ministry of Health, Labour and Welfare approved KOSTAIVE, the world’s first approved self-amplifying mRNA COVID-19 vaccine. The Japanese approval was enabled in part by a joint venture between Arcturus, CLS, Meiji Seika Pharma, and ARCALIS. The business specialized in mRNA production and delivery capacity within Japan to guarantee that the vaccine would be produced locally and delivered with little logistical slowdown.
The European Commission soon followed with the approval of KOSTAIVE in 2025. The move was a major step towards global acceptance of self-amplifying mRNA technology. The twin regulatory approvals in two large international markets provided greater legitimacy to the platform and paved the way for future mRNA-based treatments beyond infectious disease. Arcturus took the opportunity to reiterate its dual-technology strategy, marrying LUNAR® delivery with STARR® amplification as a template for preventive use.
In an effort to bolster its global vaccine pipeline, Arcturus formed several partnerships aside from ARCALIS. A highly valuable partnership for the company was with CSL Seqirus, an international vaccine manufacturer and distributor with experience in seasonal influenza vaccines. The deal, made in late 2022, centered on co-developing mRNA vaccines for COVID-19 and influenza. CSL brought commercial and manufacturing capabilities while Arcturus supplied its mRNA technology platforms. The partnership extended Arcturus’ capabilities and solidified its position in the competitive vaccine development space.
What set Arcturus apart in a busy field was its willingness to work through an idea that had not yet been popularly taken up. While Moderna and Pfizer-BioNTech set headlines for speed and volume, Arcturus worked on fewer resources but brought a technical innovation that solved some of the downsides of traditional mRNA vaccines. The self-amplifying characteristics of STARR® potentially enabled longer-duration protection and lower reactogenicity, although ongoing research continues to assess long-term efficacy and safety outcomes.
The path from research platform to approved vaccine demonstrates the larger challenges and opportunities confronting small biotech companies in times of public health crisis. Arcturus had to navigate regulatory complexity, manufacturing collaborations, international supply chain complexities, and clinical trial logistics, all with an eye to data integrity and scientific discipline. Along the way, Payne’s executive role shaped the company’s decision-making and communications strategies. His scientific background and operational management influenced how Arcturus navigated its place in the international vaccine landscape.
Success for KOSTAIVE did not signal the end of Arcturus’ journey through sa-mRNA. The company continues to investigate further applications for its self-amplifying platform, such as prospective uses in seasonal respiratory infections. With over 500 patents and applications pending around the world by 2025, Arcturus holds an intellectual property position that stands in favor of further expansion into new therapeutic categories.
Arcturus’ experience through the COVID-19 pandemic helped build the body of evidence behind RNA-based platforms for vaccine development. KOSTAIVE’s launch in Japan and the European Union gave it key case studies for the success of sa-mRNA in real-world settings. The regulatory milestones were not mere authorizations for a single product, but an assessment of an approach that promises to upend how vaccines are developed and deployed.
Joseph E. Payne’s contribution to the creation of KOSTAIVE illustrates the convergence of science, leadership, and timing that characterizes so much of contemporary biotechnology. His work in directing the course of Arcturus Therapeutics demonstrates the ways in which focused innovation and strategic partnership can impact public health globally.
