CRISPR-Cas13 Revolutionizes RNA Modification for Gene Therapy

In a groundbreaking development, researchers at the Korea Advanced Institute of Science and Technology (KAIST) have successfully harnessed the CRISPR-Cas13 system to achieve targeted RNA modification, paving the way for enhanced gene therapy applications. This innovative technology, which enables precise acetylation of specific RNA molecules in living cells, was detailed in a study published in *Nature Chemical Biology* on June 10, 2025, by a team led by Professor Won Do Heo.

The CRISPR-Cas13 system, often referred to as RNA gene scissors, has gained significant recognition in the field of gene regulation due to its ability to selectively target and modify RNA sequences. The new research demonstrates that the CRISPR-Cas13 system can precisely locate and chemically modify the desired RNA among a myriad of RNA molecules within human cells. This is especially critical as RNA plays a pivotal role in the transmission of genetic information and protein synthesis.

As Professor Heo explained, "Existing RNA chemical modification research faced difficulties in controlling specificity, temporality, and spatiality. However, this new technology allows selective acetylation of desired RNA, opening the door for accurate and detailed research into the functions of RNA acetylation." The study introduces a novel "targeted RNA acetylation system" combining Cas13 with a hyperactive variant of the NAT10 enzyme, known as eNAT10, which significantly enhances RNA acetylation activity.

Historically, the function of RNA chemical modifications has been poorly understood, particularly concerning their role in human messenger RNA (mRNA). The KAIST team's work significantly contributes to this field by demonstrating that acetylation can enhance protein production from mRNA and facilitate the translocation of RNA from the nucleus to the cytoplasm. This advancement not only clarifies the physiological roles of RNA acetylation but also suggests potential therapeutic applications.

"The RNA chemical modification technology developed in this study can be widely used as an RNA-based therapeutic agent and a tool for regulating RNA functions in living organisms in the future," said Professor Heo. The implications of this research extend to various applications in gene therapy, particularly in treating viral infections such as COVID-19, where targeted RNA modification could suppress viral RNA and regulate the expression of disease-causing genes.

The research team successfully demonstrated in vivo applicability by delivering the targeted RNA acetylation system to the livers of experimental mice using an adeno-associated virus (AAV), a common vector in gene therapy. This achievement marks the first instance demonstrating that RNA chemical modification technology can be applied in living organisms, enhancing its potential for future therapeutic strategies.

The findings from this study underscore the transformative potential of CRISPR-Cas13 technology in RNA-based therapies, offering new avenues for research and treatment in genetic disorders and infectious diseases. As the field of gene editing and modification continues to evolve, the KAIST team's innovative approach positions CRISPR-Cas13 at the forefront of biomedical research, with far-reaching implications for the future of medicine and therapy.