Researchers at Pohang University of Science and Technology (POSTECH), led by Professor Seung Soo Oh and Dr. Hyesung Jo, have developed a new method for accurately modifying specific proteins inside living cells. Their research, published in the Journal of the American Chemical Society, introduces a technique that uses a special molecule called deoxyoxanosine (dOxa) along with small molecules known as aptamers. These aptamers can recognize and target specific areas on proteins, allowing scientists to attach dOxa precisely where needed.
Previously, modifying proteins inside living organisms was difficult because existing methods often damaged the proteins, had limited effectiveness, or required genetic changes. However, the POSTECH team’s new technique allows dOxa to attach precisely to just one desired location among many possible spots on a protein, and it does so quickly and effectively. This new approach is also much more stable than traditional methods, remaining effective at room temperature for over a month.
The researchers tested their method by successfully modifying two important proteins linked to cancer—PTK7 and nucleolin—directly inside living cancer cells. This allowed them to watch how these proteins move and function in real-time, providing valuable new insights into how these proteins are involved in cancer growth. Importantly, this is the first time specific proteins have been modified in living cells without interfering with their natural activity.
This innovative technique has great potential beyond cancer research. It could enhance targeted drug treatments, improve medical imaging, and support personalized medicine. By precisely modifying specific proteins, this new method could significantly advance drug development, targeted therapies, and our overall understanding of biological processes.
References
- Jo, H., Ju, S., Kim, M., Beon, J., Jang, S. Y., Pack, S. P., Son, C. Y., Kim, J. S., & Oh, S. S. (2025). Aptamer-Guided, Hydrolysis-Resistant Deoxyoxanosine Enables Epitope- and Moiety-Selective Conjugation to Nonengineered Proteins Even in Complex Environments. Journal of the American Chemical Society, 147(11), 9328–9340. https://doi.org/10.1021/jacs.4c15674
Serra Húnter Fellow of Sociology at Universitat Rovira i Virgili.
Former DAAD-Gastprofessorin at Julius-Maximilians-Universität Würzburg