Improved Messenger RNA Stability and Biocompatibility Through Self-Gelatinizable Nucleic Acids

Area of Science:

• Biotechnology
• Materials Science
• Molecular Biology

Background:

• Messenger RNA (mRNA) therapeutics show promise but face challenges with in vivo instability and storage.
• Current lipid nanoparticle (LNP) delivery systems, while successful, can elicit immunogenic responses.
• Safer and more stable delivery platforms are needed for advanced mRNA therapies.

Purpose of the Study:

• To develop a novel, biocompatible delivery system for mRNA therapeutics.
• To address the limitations of mRNA instability and LNP immunogenicity.
• To evaluate the efficacy and safety of mRNA-loaded DNA hydrogels.

Main Methods:

• Designed DNA units were used to create self-assembling DNA hydrogels.
• Messenger RNA was loaded into the DNA hydrogel framework.
• In vitro assays were performed to assess protein expression, mRNA stability, and immunogenicity in relevant cell types (myofibroblasts and antigen-presenting cells).

Main Results:

• The DNA hydrogel demonstrated sustained mRNA-mediated protein expression in myofibroblasts.
• The hydrogel significantly enhanced resistance of mRNA to nuclease and storage degradation.
• Negligible proinflammatory cytokine production and cytotoxicity were observed in antigen-presenting cells.

Conclusions:

• mRNA-loaded DNA hydrogels represent a promising, biocompatible platform for next-generation mRNA therapeutics.
• This technology offers enhanced mRNA stability and reduced immunogenicity compared to existing methods.
• DNA hydrogels provide a viable alternative for developing safer and more effective mRNA-based treatments.