mRNA Delivery by a pH-Responsive DNA Nano-Hydrogel

Area of Science:

• Biotechnology
• Nanotechnology
• Molecular Biology

Background:

• Messenger RNA (mRNA) holds therapeutic potential, overcoming risks associated with transgenes.
• Existing mRNA delivery vehicles lack optimal expression efficiency and biocompatibility.

Purpose of the Study:

• To develop a DNA nano-hydrogel system for efficient and biocompatible mRNA delivery.
• To achieve effective protein expression comparable to commercial liposomes but with enhanced safety.

Main Methods:

• Fabrication of a DNA nano-hydrogel system composed entirely of DNA, excluding the mRNA payload.
• Compaction of the nano-hydrogel into nanospheres via DNA scaffolds and linkers for cellular uptake via endocytosis.
• Integration of a pH-responsive i-motif structure for controlled intracellular mRNA release.

Main Results:

• The DNA nano-hydrogel demonstrated superior biocompatibility compared to chemical delivery vehicles.
• Efficient cellular delivery and endocytosis facilitated by the nanosphere structure.
• High mRNA translation efficiency into proteins, comparable to commercial liposomes, due to effective delivery and release.

Conclusions:

• The developed DNA nano-hydrogel system provides an efficient and highly biocompatible platform for mRNA delivery.
• This system shows significant potential as a competitive alternative for in vivo functional mRNA delivery.