美国莱斯大学Jerzy O. Szablowski研究团队开发出用于无创监测大脑基因表达的工程血清标记物。该研究于2024年1月10日发表于国际一流学术期刊《自然—生物技术》杂志上。

他们介绍了一种非侵入性、多路、位点特异性监测内源性基因或转基因在大脑中的表达的方法，该方法通过称为释放活性标记(RMA)的工程报告器进行监测。RMA由易于检测的报告蛋白和受体结合结构域组成，受体结合结构域可使胞吞作用跨越脑内皮。RMA在大脑中表达，但进入血液，在那里它们很容易被测量。他们的研究表明，在一个约占大脑体积1%的小鼠大脑部位表达RMA，可以提供比基线高10万倍的信号增加。

RMA在数十到数百个神经元中的表达足以可靠地检测它们。他们证明，与未激活对照相比，表达Fos反应性RMA的细胞的化学发生激活使血清RMA水平增加了6倍以上。RMA提供了一种非侵入性的方法，可重复，多路监测完整动物大脑中的基因表达。

据悉，大脑中基因表达的测量需要对脑组织进行侵入性分析或非侵入性方法，这些方法由于灵敏度低而受到限制。

附：英文原文

Title: Engineered serum markers for non-invasive monitoring of gene expression in the brain

Author: Lee, Sangsin, Nouraein, Shirin, Kwon, James J., Huang, Zhimin, Wojick, Jessica A., Xia, Boao, Corder, Gregory, Szablowski, Jerzy O.

Issue&Volume: 2024-01-10

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.

DOI: 10.1038/s41587-023-02087-x

Source: https://www.nature.com/articles/s41587-023-02087-x