Scientific reportsOct 1, 2025

Design and testing of a valine-enhanced lipid nanoparticle mRNA vaccine targeting the COVID-19 spike protein receptor site

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

A valine-added lipid nanoparticle construct targeting SARS-CoV-2 RBD was built and showed favorable physical characterization and early biological signals.

Evidence

This formulation/platform experiment used in silico design, in vitro transcription, spectroscopic, thermal, microscopic, size, surface-tension, cytotoxicity, and qPCR assays to characterize a sub-100 nm LNP-coated mRNA vaccine that was not cytotoxic and increased IFNA1, IFNB1, and TNF expression.

Caveat

The abstract reports preclinical characterization only, with no animal challenge, human immune-response, efficacy, durability, or safety outcomes.

Simplified

The SARS-CoV-2 pandemic has led to major advances in development. This study aimed to develop a cationic lipid nanoparticle (LNP) coated mRNA vaccine targeting the receptor binding domain (RBD) against the SARS-CoV-2 virus and adding valine to the N-terminal end to increase its stability, and to comprehensively characterize the physical, thermal, microscopic and biological properties of vaccine. The vaccine was designed in silico and valine-added S-RBD molecule was generated by IVT. The LNP coated mRNA vaccine was evaluated by spectroscopic (UV-vis, FT-IR, Raman), thermodynamic (TGA/DSC), microscopic (STEM, AFM), size/potential (DLS) and surface tension analysis methods. The developed vaccine was analyzed for cytotoxicity (MTT) and pro/anti-inflammatory gene expression (qPCR). Spectroscopic analyses revealed distinct RNA and lipid peaks. Thermodynamic analyses revealed complete mass loss for mRNA and LNP at 136.2 °C and 85.7 °C, respectively. STEM analysis revealed that mRNA was uniformly coated with LNP, and its size was < 100 nm, and Ra/Rz values were 26.56/34.29 nm, respectively. Zeta potentials ranged from 0 to - 30 mV, and surface tensions were 33.8-38.0 mN/m, respectively. MTT analysis showed that the vaccine was not cytotoxic. qPCR analysis, significant increases were detected in IFNA1, IFNB1 and TNF gene expressions, but no significant increase was detected in IL6. Bioinformatic analyses revealed increased stability in mRNA structure and more robust pseudoknot formations after valine addition. Our study is the first study in which a uniquely designed valine-added mRNA vaccine coated with LNP targeting the RBD antigen of SARS-CoV-2 was developed and comprehensively characterized.

Key numbers

136.2 °C

Complete mass loss temperature for

Temperature at which shows complete degradation.

85.7 °C

Complete mass loss temperature for without

Temperature at which shows complete degradation.

−17.68 to −25.09 mV

range of vaccine formulations

values indicating stability of .

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Design and testing of a valine-enhanced lipid nanoparticle mRNA vaccine targeting the COVID-19 spike protein receptor site

Abstract

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