Efficient Delivery of mRNA Using Crosslinked Nucleic Acid Nanogel as a Carrier

In vitro-transcribed messenger RNA (mRNA) can efficiently express the therapeutic proteins in target cells without the concern of mutagenesis, which holds great promise for the treatment of a broad range of diseases. However, the safe and effective delivery of mRNA remains a challenge and the development of novel delivery vehicles is highly desirable. Herein, a nucleic acid nanogel-based mRNA delivery system is designed and prepared for robust mRNA-encoding gene expression, which can efficiently produce the interested proteins and realize the proteins’ functions in situ. Via simple nucleic acid hybridization, we demonstrate the efficient loading of either the enhanced green fluorescence protein-encoded mRNA (EGFP-mRNA) or Cas9 protein-encoded mRNA (Cas9-mRNA) in a nucleic acid nanogel, which can effectively enter the cells and results in robust EGFP expression or CRISPR/Cas9-mediated genome editing. This study provides a novel and general mRNA delivery platform that has the potential to deliver various mRNA-encoding therapeutic proteins for biomedical purposes.