Synthetic Strategy for mRNA Encapsulation and Gene Delivery with Nanoscale Metal-Organic Frameworks

Area of Science:

• Biomedical engineering
• Materials science
• Nanotechnology

Background:

• Metal-organic frameworks (MOFs) are transitioning from traditional applications to advanced biomedical uses, including drug delivery.
• While MOFs have been used for small molecule and nucleic acid delivery (DNA, siRNA), messenger RNA (mRNA) delivery remains unexplored.

Purpose of the Study:

• To address the gap in mRNA delivery using MOFs by developing a system for encapsulating and delivering mRNA.
• To investigate the potential of zeolitic imidazole framework-8 (ZIF-8) for mRNA delivery and storage.

Main Methods:

• Identified synthetic conditions for encapsulating mRNA within ZIF-8.
• Developed a core-shell particle by incorporating polyethyleneimine (PEI) to stabilize mRNA within the ZIF-8 structure.
• Evaluated protein expression in cell lines and in vivo (mice) and assessed mRNA stability under various storage conditions.

Main Results:

• Successfully encapsulated mRNA within ZIF-8, overcoming initial instability in biological media through PEI complexation.
• Achieved effective protein expression in multiple cell lines and in mice, comparable to commercial lipid-based delivery systems.
• Demonstrated successful protein expression after three months of room-temperature storage in vitro and one month in vivo, indicating thermal stability.

Conclusions:

• The developed PEI-ZIF-8 system represents the first demonstration of MOF-based mRNA encapsulation and delivery.
• This approach offers a robust platform for therapeutic mRNA delivery and opens new possibilities for long-term, temperature-stable mRNA storage and transport.