Sangsin Lee

All Publications

• 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