Objective:

To develop a modular platform for delivering RNA therapeutics as an alternative to lipid nanoparticle systems.

Key Findings:

• The supramolecular polycations form 'supra-polyplex' nanoparticles with RNA through electrostatic interactions.
• Particles were typically below 150 nm with low polydispersity.
• Nanoparticles delivered mRNA with transfection efficiencies comparable to commercial reagents while maintaining high cellular viability.
• The system is adaptable to multiple RNA classes, effectively delivering siRNA and self-amplifying RNA.

Interpretation:

This modular platform offers a flexible and scalable alternative for RNA delivery, potentially enhancing the effectiveness of RNA therapies and expediting vaccine development.

Limitations:

• Further mechanistic studies are needed to understand the influence of supramolecular architecture on intracellular trafficking and RNA release.

Conclusion:

The platform could support faster development of RNA-based vaccines and expand treatment options for various diseases.