mRNA incorporation of C(5)-halogenated pyrimidine ribonucleotides and induced high expression of corresponding protein for the development of mRNA vaccine.

In this report, we present our studies on mRNA, which was modified by introducing various halogen substituents at the C(5) position of the pyrimidine base. Specifically, we synthesized C(5)-halogenated (F, Cl, Br, I) pyrimidine ribonucleoside triphosphates and incorporated them into mRNA during in-vitro transcription. The efficiency of the in-vitro transcription reaction of halogenated pyrimidine was observed to decrease as the size of the halogen substituent increased and the electronegativity thereof decreased (F > Cl > Br) except for iodine. Interestingly, we found that, among the C(5)-halogenated pyrimidine ribonucleotides, mRNA incorporating C(5)-halogenated cytidine (5-F rCTP and 5-Cl rCTP) exhibited more prominent protein expression than mRNA modified with C(5)-halogenated uridine and unmodified mRNA. In particular, in the case of mRNA to which fluorine (5-F rCTP) and chlorine (5-Cl rCTP) were introduced, the protein was dramatically expressed about 4 to 5 times more efficiently than the unmodified mRNA, which was similar to pseudouridine (ψ). More interestingly, when pseudouridine(ψ) and fluorocytidine nucleotides (5-F rCTP), were simultaneously introduced into mRNA for dual incorporation, the protein expression efficiency dramatically increased as much as tenfold. The efficiency of cap-dependent protein expression is much higher than the IRES-dependent (internal ribosome entry site) expression with mRNA incorporating C(5)-halogenated pyrimidine ribonucleotide. We expect these results to contribute meaningfully to the development of therapeutics based on modified mRNA.

Molecular Dipoles as a Surface Flattening and Interface Stabilizing Agent for Lithium-Metal Batteries.

Reaching the border of the capable energy limit in existing battery technology has turned research attention away from the rebirth of unstable Li-metal anode chemistry in order to achieve exceptional performance. Strict regulation of the dendritic Li surface reaction, which results in a short circuit and safety issues, should be achieved to realize Li-metal batteries. Herein, this study reports a surface-flattening and interface product stabilizing agent employing methyl pyrrolidone (MP) molecular dipoles in the electrolyte for cyclable Li-metal batteries. The excellent stability of the Li-metal electrode over 600 cycles at a high current density of 5 mA cm-2 has been demonstrated using an optimal concentration of the MP additive. This study has identified the flattening surface reconstruction and crystal rearrangement behavior along the stable (110) plane assisted by the MP molecular dipoles. The stabilization of the Li-metal anodes using molecular dipole agents has helped develop next-generation energy storage devices using Li-metal anodes, such as Li-air, Li-S, and semi-solid-state batteries.