mRNA delivery enabled by metal-organic nanoparticles.

Area of Science:

• Biotechnology
• Materials Science
• Nanomedicine

Background:

• Messenger RNA (mRNA) therapeutics offer revolutionary potential for disease treatment and prevention.
• Current mRNA delivery systems face limitations, including poor organ specificity and inflammatory responses associated with cationic components.
• Developing safe, effective, and targeted mRNA delivery platforms is crucial for advancing therapeutic applications beyond vaccines.

Purpose of the Study:

• To engineer a versatile, noncationic nanoparticle platform for enhanced mRNA delivery.
• To address challenges of limited organ tropism and inflammation in current mRNA delivery systems.
• To create a modular approach for assembling mRNA therapeutics with tunable organ targeting.

Main Methods:

• Assembly of mRNA into a poly(ethylene glycol)-polyphenol network stabilized by metal ions.
• Screening of various components and compositional ratios to generate a library of metal-organic nanoparticles.
• In vitro and in vivo (mice) evaluation of mRNA transfection efficiency and biocompatibility.
• Assessment of organ tropism following intravenous administration by varying nanoparticle composition.

Main Results:

• A library of stable, noncationic, and highly biocompatible metal-organic nanoparticles was successfully generated.
• Robust mRNA transfection was achieved in vitro and in vivo.
• Intravenous administration led to predominant protein expression and gene editing in the brain, liver, and kidney.
• Organ tropism was successfully tuned by modifying nanoparticle composition.

Conclusions:

• The developed metal-organic nanoparticle platform provides a versatile and noncationic approach for mRNA delivery.
• This platform overcomes key limitations of existing mRNA delivery systems, enabling targeted delivery and reducing inflammation.
• The findings open new avenues for metal-organic nanoparticle-enabled mRNA therapeutics with tunable organ tropism for various health applications.