Zn²⁺ -Coordination-Driven RNA Assembly with Retained Integrity and Biological Functions

Area of Science:

• Coordination chemistry
• Nanobiotechnology
• RNA therapeutics

Background:

• Metal-coordination-directed crosslinking is established for DNA, peptides, proteins, and polysaccharides.
• RNA biopolymers have been avoided due to stability concerns and potential functional alterations.

Purpose of the Study:

• To report the first instance of Zn2+-driven RNA self-assembly into stable nanoparticles.
• To demonstrate the retention of RNA integrity and biological function post-assembly.
• To explore the therapeutic potential of these novel RNA nanostructures.

Main Methods:

• Utilized Zn2+ ions to induce self-assembly of various functional RNAs (20-1000 nucleotides).
• Characterized the resulting spherical RNA nanoparticles.
• Evaluated RNA loading efficiency, pharmacokinetics, and bioavailability.
• Assessed in vitro and in vivo efficacy for mRNA and microRNA delivery.

Main Results:

• Successfully formed stable, spherical RNA nanoparticles using Zn2+.
• Achieved superior RNA-loading efficiency, pharmacokinetics, and bioavailability.
• Demonstrated effective mRNA delivery for GFP protein expression.
• Showcased microRNA delivery for triple-negative breast cancer treatment.

Conclusions:

• Zn2+-driven RNA self-assembly offers a versatile method for creating functional RNA nanoparticles.
• This approach overcomes previous limitations in RNA biopolymer synthesis.
• The developed RNA nanospheres significantly expand the applications of RNA coordination chemistry and RNA-based therapeutics.