加州理工学院Mikhail G. Shapiro小组近日取得一项新成果。经过不懈努力，他们研究出基因表达的多路超声成像。相关论文于2025年11月18日发表于国际顶尖学术期刊《自然—方法学》杂志上。

在这里，该课题组研究人员以合理的蛋白质设计为主题和定向进化，开发出两种新的ARGs，它们可以根据它们的共色压力响应谱相互区分，从而实现基因表达的“双音”超声成像。研究团队展示了多重ARGs在体外描绘细菌细胞种类和细胞状态的效用，然后将其应用于对非主题胃肠道中益生菌的不同亚群和体内肿瘤定殖细菌的成像。正如荧光蛋白的第一个波长偏移衍生物为光学显微镜开辟了一个生动的世界一样，他们的下一代光学蛋白为来自活体的超声信号的丰富交响曲奠定了基础。

据悉，光学报告基因（ARGs）使超声成像基因表达成为可能，从而提供了对深层、光学不透明的活组织的高分辨率访问。然而，与它们的荧光对应物不同，ARG迄今为止仅限于单一的“声音”，无法对细胞状态或群体进行多路成像。

附：英文原文

Title: Multiplexed ultrasound imaging of gene expression

Author: Nystrm, Nivin N., Jin, Zhiyang, Bennett, Marisa E., Zhang, Ruby, Swift, Margaret B., Shapiro, Mikhail G.

Issue&Volume: 2025-11-18

Abstract: Acoustic reporter genes (ARGs) have enabled imaging of gene expression with ultrasound, which provides high resolution access to deep, optically opaque living tissues. However, unlike their fluorescent counterparts, ARGs have so far been limited to a single ‘sound’, preventing multiplexed imaging of cellular states or populations. Here we use rational protein design and directed evolution to develop two new ARGs that can be distinguished from each other based on their acoustic pressure-response profiles, enabling ‘two-tone’ ultrasound imaging of gene expression. We demonstrate the utility of multiplexed ARGs for delineating bacterial cell species and cell states in vitro, and then apply them towards imaging distinct subpopulations of probiotics in the mouse gastrointestinal tract and of tumor-colonizing bacterial agents in vivo. Just as the first wavelength-shifted derivatives of fluorescent proteins opened a vivid world for optical microscopy, our next-generation acoustic proteins set the stage for a rich symphony of ultrasound signals from living subjects.

DOI: 10.1038/s41592-025-02825-w

Source: https://www.nature.com/articles/s41592-025-02825-w