Sangsin Lee

All Publications

• Enzyme miniaturization: Revolutionizing future biocatalysts. Biotechnology advances Ding, N., Jiang, Y., Lee, S., Cheng, Z., Ran, X., Ding, Y., Ge, R., Zhang, Y., Yang, Z. J. 2025: 108598

  Abstract

  Enzyme miniaturization offers a transformative approach to overcome limitations posed by the large size of conventional enzymes in industrial, therapeutic, and diagnostic applications. However, the evolutionary optimization of enzymes for activity and stability has not inherently favored compact structures, creating challenges for modern applications requiring smaller and more efficient catalysts. In this review, we surveyed the advantages of miniature enzymes, including enhanced expressivity, folding efficiency, thermostability, and resistance to proteolysis. We described the applications of miniature enzymes as biosensors, therapeutic agents, and industrial catalysts. We highlighted strategies such as genome mining, rational design, random deletion, and de novo design for achieving enzyme miniaturization, integrating both computational and experimental techniques. By investigating these approaches, we aim to provide a framework for advancing enzyme engineering, emphasizing the unique potential of smaller enzymes to revolutionize biocatalysis, gene therapy, and biosensing technologies.

  View details for DOI 10.1016/j.biotechadv.2025.108598

  View details for PubMedID 40354901

• Engineered serum markers for non-invasive monitoring of gene expression in the brain NATURE BIOTECHNOLOGY Lee, S., Nouraein, S., Kwon, J. J., Huang, Z., Wojick, J. A., Xia, B., Corder, G., Szablowski, J. O. 2024; 42 (11): 1717-1725

  Abstract

  Measurement of gene expression in the brain requires invasive analysis of brain tissue or non-invasive methods that are limited by low sensitivity. Here we introduce a method for non-invasive, multiplexed, site-specific monitoring of endogenous gene or transgene expression in the brain through engineered reporters called released markers of activity (RMAs). RMAs consist of an easily detectable reporter and a receptor-binding domain that enables transcytosis across the brain endothelium. RMAs are expressed in the brain but exit into the blood, where they can be easily measured. We show that expressing RMAs at a single mouse brain site representing approximately 1% of the brain volume provides up to a 100,000-fold signal increase over the baseline. Expression of RMAs in tens to hundreds of neurons is sufficient for their reliable detection. We demonstrate that chemogenetic activation of cells expressing Fos-responsive RMA increases serum RMA levels >6-fold compared to non-activated controls. RMAs provide a non-invasive method for repeatable, multiplexed monitoring of gene expression in the intact animal brain.

  View details for DOI 10.1038/s41587-023-02087-x

  View details for Web of Science ID 001140277600001

  View details for PubMedID 38200117

  View details for PubMedCentralID PMC11233427