A domestic research team has developed a technology that can accurately find and chemically modify only the desired ribonucleic acid (RNA) among countless RNAs in cells for the first time in the world.
A research team led by Professor Heo Won-do of the Korea Advanced Institute of Science and Technology (KAIST) has developed a technology to acetylate specific RNA in the body using the CRISPR gene-editing tool (CRISPR-Cas13), as announced on the 10th. The research results were published in the international journal "Nature Chemical Biology" on the 2nd.
Genes are formed by a connection of four types of bases. They determine life phenomena by synthesizing proteins in this order. Decoding genes is the process of confirming these base sequences. The genetic information of DNA is copied into RNA and used for protein synthesis.
RNA itself does not change its base sequence but can change its characteristics and functions through a process known as "chemical modification," where other chemicals are added. In the case of one such chemical modification, N4-acetylcytidine, it has not been precisely known what function this modification performs within cells.
In particular, there has been controversy regarding whether this modification actually exists in the messenger RNA (mRNA) of human cells and what role it plays. mRNA is the RNA that serves as a blueprint for synthesizing proteins in the body.
To clarify the role of acetylation, the research team developed a "target RNA acetylation system (dCas13-eNAT10)" that combines components for RNA acetylation with the CRISPR gene-editing tool, Cas13, which precisely targets the desired RNA. The CRISPR gene-editing tool is an enzyme complex that selects and cuts specific genes. This is the technology that accurately selects specific RNA and adds acetyl groups.
The research team confirmed that they could cause chemical modifications by attaching acetyl groups to the desired RNA using the target RNA acetylation system. They also confirmed that protein production increased in acetylated mRNA. Furthermore, they revealed for the first time that RNA acetylation helps move RNA from the nucleus to the cytoplasm. This demonstrates that chemical modifications of acetylation can regulate the location of RNA within cells.
The research team subsequently demonstrated that the developed system could deliver the system to the liver of experimental mice through viral vectors, which are widely used in gene therapy, proving that precise regulation of RNA acetylation is possible within living organisms. They noted that this is the first case showing that the technology to chemically modify RNA can be applied in vivo.
Professor Heo Won-do said, "Existing RNA chemical modification studies were difficult in specificity, timing, and spatial regulation, but this technology allows selective acetylation of the desired RNA, opening the way to accurately and meticulously study the functions of RNA acetylation." He added, "The RNA chemical modification technology developed this time could be widely utilized as a tool for RNA-based therapeutics and for regulating RNA functions in vivo."
References
Nature Chemical Biology (2025), DOI: https://doi.org/10.1038/s41589-025-01922-3