Abstract: Provided is a SARS-CoV-2 mRNA vaccine, and the preparation method and use thereof. The present invention provides an mRNA molecule capable of encoding a target polypeptide, wherein the target polypeptide comprises an NTD-RBD natural domain in the Spike (S) protein of SARS-CoV-2, and wherein the NTD-RBD natural domain comprises an NTD fragment and an RBD fragment, the NTD fragment and the RBD fragment being linked together via a natural amino acid sequence derived from the S protein as a linker. The present invention provides an mRNA encoding a NTD-RBD natural domain in the Spike protein of SARS-CoV-2, which achieves an immune effect against SARS-CoV-2 mutant strains and is widely applicable.

Abstract: Disclosed herein are an mRNA targeting molecule comprising an N-acetylgalactosamine binding polypeptide and a preparation method therefor. A plasmid vector containing a DNA fragment formed by sequentially connecting a promoter, a target gene, a specific protease cleavage sequence, and a polynucleotide sequence encoding a GBD capable of binding to N-acetylgalactosamine, is transcribed to obtain an mRNA, which is connected to a DNA-puromycin linker under the action of a T4 ligase. The resulting connection product is subjected to protein translation, followed by cleavage using a specific protease to obtain an mRNA-puromycin-GBD complex, which then binds to a GBD protein sequence under the action of an N-acetylgalactosamine transferase to form an mRNA-puromycin-GBD-GalNAc complex, thereby modifying the mRNA with GalNAc, thus achieving the purpose of precise administration in a process of mRNA drug delivery and increasing the efficacy of the mRNA drug molecule.

Abstract: The present invention provides a mannose-based mRNA targeted delivery system and use thereof. The mRNA can encode one or more target polypeptides and contains at least one mannose modification. The technical solution of the present invention modifies the mRNA molecule with a mannose, so that the mRNA can be directly and efficiently coupled with the mannose, and the targeted delivery of the mRNA is realized without the need for a carrier.