A next-generation mRNA platform that maintains efficacy in elderly and obese patients has been developed in South Korea.
KAIST announced on January 10 that a joint research team led by Professor Lee Young-seok from KAIST's Department of Bio and Brain Engineering and Professor Nam Jae-hwan from Catholic University of Korea has developed a new mRNA platform through precision engineering of the '5′ untranslated region (5′UTR)' sequence, a key regulatory region of mRNA.
mRNA vaccines work by delivering genetic information that instructs cells to produce specific proteins, thereby generating therapeutic effects. The 5′ untranslated region is the segment of mRNA that initiates and regulates protein production efficiency, and its design can affect both the quantity and speed of protein synthesis.
By redesigning this region, the research team enhanced therapeutic protein production efficiency and overcame previous limitations of reduced efficacy in aging and obese conditions. In aging and obese states, cells experience high oxidative stress, which can impair their ability to produce proteins.
The research team analyzed extensive biodata to identify 5′UTR sequences that enable more efficient protein production across various cellular environments. The process utilized multiple analytical techniques including large-scale tissue transcriptome analysis (RNA-seq) for measuring gene activity, single-cell transcriptome analysis (scRNA-seq) for examining gene expression at individual cell levels, and ribosome profiling (Ribo-seq) for measuring actual protein production efficiency.
When the new mRNA therapeutics incorporating the identified high-performance 5′UTR sequences were applied to preclinical models of aging and obesity, significant improvements in protein production and immune response were observed in cells.
This research is expected to be applicable not only to mRNA vaccines but also to the development of various biopharmaceutical technologies including gene therapies and immunotherapies.
"This research identified design methods that enable mRNA to produce proteins more effectively by analyzing extensive biological data," said Professor Lee Young-seok. "This technology will serve as an important foundation for ensuring that mRNA vaccines and therapeutics work effectively even in environments where drug efficacy may be reduced, such as in elderly or obese patients."
The research, with Dr. Yoon Su-bin of Catholic University of Korea and KAIST doctoral student Cho Hyung-gon as co-first authors, was published online on January 2 in Molecular Therapy (IF=12.0), a leading journal in gene and cell therapy.
The research was supported by the Ministry of Science and ICT's National Research Foundation of Korea's Excellent Young Researcher Program and Bio-Medical Development Project, the Ministry of Food and Drug Safety's Innovative Technology Support Research for Infectious Disease Response, and the Korea Health Industry Development Institute's Infectious Disease Prevention and Treatment Technology Development Project.