Fig. 10: Graphical comparison between conventional mRNA and Gemini platforms.

Challenges of Conventional mRNA Vaccines: Although conventional mRNA vaccines were instrumental in mitigating COVID-19 mortality, their widespread deployment was constrained by technological hurdles such as limited molecular stability, complex and intricate manufacturing processes, and a dependency on lipid nanoparticle (LNP) encapsulation, which posed challenges for production, storage, and global distribution, particularly in resource-limited settings. Overview of Gemini Platform: The Gemini platform represents a novel innovation that employs a bifunctional eukaryotic–prokaryotic promoter, functioning both as a self-amplifying RNA (saRNA) and a self-amplifying DNA (saDNA) replicon, thereby enabling robust amplification and expression of genetic cargo while addressing key limitations of conventional mRNA vaccines. Stability and Storage: Unlike conventional mRNA vaccines that degrade after one freeze-thaw cycle, Gemini demonstrates exceptional stability through five freeze-thaw cycles and can be freeze-dried for powder storage and aqueous reconstitution. LNP Elimination: A critical advantage is bypassing LNP encapsulation requirements essential for conventional mRNA vaccines, simplifying manufacturing, reducing costs, and mitigating LNP-associated toxicity and adverse reactions. Cold Chain Management: While LNP-mRNA vaccines require -20°C to −80°C storage, Gemini formulations remain stable at 2°C to 8°C, reducing logistical challenges in remote settings. Extended Protein Expression: Gemini offers prolonged protein expression exceeding 28 days versus 3 days for conventional mRNA, supporting robust sustained immune responses including humoral antibodies and T-cell responses. Payload Capacity: Capacity reaches 16−20 kb, far exceeding mRNA’s 4 kb limit, enabling complex protein expression and multivalent vaccine development. Safety and Integration: The safety profiles are highly favourable, with integration risks at least five orders of magnitude below FDA-established safety limits. Naked Gemini formats elicit durable antibody responses and demonstrate potential for reducing SARS-CoV-2 viremia and limiting transmission. (Created in BioRender. Fan J. (2025) https://BioRender.com/lrkpjt4).