A binary self-amplifying expression platform enabling lipid nanoparticle-free vaccines and nanomedicines

Area of Science:

• Molecular Biology
• Vaccinology
• Biotechnology

Background:

• Conventional mRNA vaccines are crucial but face challenges like instability, limited payload, and complex manufacturing using lipid nanoparticles (LNPs).
• Addressing these limitations is key for developing more effective and accessible vaccine technologies.

Purpose of the Study:

• To introduce the Gemini platform, a novel expression system for self-amplifying RNA (saRNA) and self-amplifying DNA (saDNA) replicons.
• To demonstrate Gemini's advantages over conventional mRNA vaccines, including enhanced stability, simplified manufacturing, and broader payload capacity.

Main Methods:

• Development of a bifunctional eukaryotic-prokaryotic promoter for the Gemini platform.
• Evaluation of Gemini's stability under various conditions (freeze-thaw, lyophilization) and its storage compatibility.
• Assessment of Gemini's payload capacity and protein expression duration.
• Development and testing of a single-dose SARS-CoV-2 vaccine based on the Gemini platform.

Main Results:

• The Gemini platform enables robust amplification and expression of genetic cargo as either saRNA or saDNA.
• Gemini eliminates the need for LNPs, shows enhanced stability, and allows ambient-temperature storage.
• Demonstrated a potent single-dose SARS-CoV-2 vaccine inducing prolonged protein expression.
• Gemini supports larger, more complex payloads compared to conventional mRNA vaccines.

Conclusions:

• The Gemini platform is a versatile, next-generation expression system overcoming key limitations of current mRNA vaccines.
• Its stability, simplified manufacturing, and flexibility offer significant advantages for molecular medicine and pandemic preparedness.
• Gemini represents a promising advancement in vaccine technology with broad applicability.