通过基因编码的MRI记者基因在肝脏中对rAAV介导的基因表达的非侵入性跟踪

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Zinia Mohanta¹, Aruna Singh¹, Hernando Lopez-Bertoni²

¹Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA.

Molecular therapy : the journal of the American Society of Gene Therapy

|November 14, 2025

概括

这项研究介绍了superCESTide,这是一种新的基因编码记者,用于基因表达的非侵入性成像. 这种化学交换和转移 (CEST) MRI 方法允许在没有外部对比剂的情况下跟踪复合腺相关病毒 (rAAV) 基因治疗.

科学领域:

生物医学成像技术生物医学成像技术
分子成像学分子成像学
基因治疗基因治疗

背景情况:

对基因表达的非侵入性成像对基因治疗至关重要,但仍然具有挑战性.
目前的方法通常需要外源的对比剂,限制了它们的应用.
需要强大的体内记者来监测转基因表达.

研究的目的:

为了证明第一个基因编码的化学交换和转移 (CEST) MRI报告员的体内应用.
评估超CESTide报告员对监测复合腺相关病毒 (rAAV) 中介基因表达的疗效.
建立CESTMRI作为成像引导基因疗法的非侵入性工具.

主要方法:

在小鼠中,对编码超CESTide 记者和 tdTomato 光记者的 rAAV 进行全身注射.
使用CEST MRI,光成像和逆转录PCR进行评估.
对剂量依赖的信号增强和与记者表达的相关性进行分析.

主要成果:

CEST MRI显示肝脏显著,剂量依赖的信号增强.
在CEST对比度和超CESTide表达之间观察到强烈的相关性 (r = 0.75,p < 0.05).
最高的rAAV剂量导致最强的MTR_asym信号,通过组图分析确定了明显的表达模式.

结论:

基因编码的超CESTide可以通过CESTMRI无需外源药物进行转基因表达的非侵入性检测.
验证了CESTMRI作为一种强大的工具来监测rAAV介导的基因表达 in vivo.
这种方法为成像引导的基因疗法应用开辟了新的途径.

关键词:

在CEST中,CEST是CEST.这就是为什么MRI是MRI.化学交换和转移化学交换和转移基因表达的基因表达方式基因监测基因监测基因监测分子成像分子成像技术在临床前的临床前.rAAAVAV 在这里.记者基因记者基因翻译工作的翻译工作.

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Reporter Genes

Reporter Genes

Reporter genes are a type of protein-coding gene that are often tagged to a gene of interest. Once inside a target cell, reporter genes usually produce visually identifiable characteristics like fluorescence and luminescence when expressed along with the gene of interest. Thus, reporter genes “report” the presence or absence of genes of interest in an organism, determine the gene expression pattern, or track the physical location of a DNA segment or protein in the cell.