小柯机器人

美国加州理工学院Mikhail G. Shapiro研究组报道了基因组挖掘声学报告基因(ARGs)，用于实时监测肿瘤和肿瘤归巢细菌。相关论文发表在2023年1月2日出版的《自然—生物技术》杂志上。

他们描述了两个ARG——一个用于细菌，一个用于哺乳动物细胞——通过来自不同细菌和古生菌的候选气囊泡基因簇的系统发育筛选确定，这些基因簇提供了更强的超声对比度，产生与背景组织不同的非线性信号，并能够稳定长期表达。与第一代相比，这些改进的细菌和哺乳动物ARG分别产生9倍和38倍的非线性对比度。使用这些新的ARG，他们在肿瘤回巢治疗细菌中进行了原位肿瘤定植和基因表达的非侵入性成像，追踪了乳腺癌小鼠模型中肿瘤基因表达和生长的进展，并对基因镶嵌肿瘤进行了基因表达引导的针活检，证明了在厘米深处无侵入性地获得动态生物学过程。

据介绍，与光学方法相比，超声可以在更大的深度进行成像，但现有的用于体内细胞成像的基因编码声波报告因子由于灵敏度、特异性和体内表达差而受到限制。

附：英文原文

Title: Genomically mined acoustic reporter genes for real-time in vivo monitoring of tumors and tumor-homing bacteria

Author: Hurt, Robert C., Buss, Marjorie T., Duan, Mengtong, Wong, Katie, You, Mei Yi, Sawyer, Daniel P., Swift, Margaret B., Dutka, Przemysaw, Barturen-Larrea, Pierina, Mittelstein, David R., Jin, Zhiyang, Abedi, Mohamad H., Farhadi, Arash, Deshpande, Ramya, Shapiro, Mikhail G.

Issue&Volume: 2023-01-02

Abstract: Ultrasound allows imaging at a much greater depth than optical methods, but existing genetically encoded acoustic reporters for in vivo cellular imaging have been limited by poor sensitivity, specificity and in vivo expression. Here we describe two acoustic reporter genes (ARGs)—one for use in bacteria and one for use in mammalian cells—identified through a phylogenetic screen of candidate gas vesicle gene clusters from diverse bacteria and archaea that provide stronger ultrasound contrast, produce non-linear signals distinguishable from background tissue and have stable long-term expression. Compared to their first-generation counterparts, these improved bacterial and mammalian ARGs produce 9-fold and 38-fold stronger non-linear contrast, respectively. Using these new ARGs, we non-invasively imaged in situ tumor colonization and gene expression in tumor-homing therapeutic bacteria, tracked the progression of tumor gene expression and growth in a mouse model of breast cancer, and performed gene-expression-guided needle biopsies of a genetically mosaic tumor, demonstrating non-invasive access to dynamic biological processes at centimeter depth.

DOI: 10.1038/s41587-022-01581-y

Source: https://www.nature.com/articles/s41587-022-01581-y

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex