Expanding salivary biomarker detection by creating a synthetic neuraminic acid sensor via chimeragenesis.

Samuel J Verzino, Sharona A Priyev, Valeria A Sánchez Estrada, Ali GholamianMogaddan, Gemma X Crowley, Alexandra Rutkowski, Amelia C Lam, Elizabeth S Nazginov, Paola Kotemelo, Agustina Bacelo, Jack D Flannery, Ksenya Gavrilov, Desiree T Sukhram, Frank X Vázquez, Javier F Juárez
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Abstract

Accurate and timely diagnosis of oral squamous cell carcinoma (OSCC) is crucial in preventing its progression to advanced stages with poorer prognosis. As such, the construction of sensors capable of detecting previously established disease biomarkers for the early and non-invasive diagnosis of this and many other conditions has enormous therapeutic potential. In this work, we apply synthetic biology techniques for the development of a whole-cell biosensor (WCB) that leverages the physiology of engineered bacteria in vivo to promote the expression of an observable effector upon detection of a soluble molecule. To this end, we have constructed a bacterial strain expressing a novel chimeric transcription factor (Sphnx) for the detection of N-acetyl-D-neuraminic acid (Neu5Ac), a salivary biomolecule correlated with the onset of OSCC. This WCB serves as the proof-of-concept of a platform that can eventually be applied to clinical screening panels for a multitude of oral and systemic medical conditions whose biomarkers are present in saliva.

通过嵌合基因工程合成神经氨酸传感器,扩大唾液生物标记物检测范围。
准确及时地诊断口腔鳞状细胞癌(OSCC)对于防止其发展到预后不良的晚期阶段至关重要。因此,构建能够检测先前确定的疾病生物标志物的传感器,用于该疾病和许多其他疾病的早期无创诊断,具有巨大的治疗潜力。在这项工作中,我们应用合成生物学技术开发了一种全细胞生物传感器(WCB),它利用体内工程细菌的生理特性,在检测到可溶性分子时促进可观察到的效应物的表达。为此,我们构建了一种表达新型嵌合转录因子(Sphnx)的细菌菌株,用于检测N-乙酰神经氨酸(Neu5Ac),这是一种与OSCC发病相关的唾液生物分子。该 WCB 是一个平台的概念验证,最终可应用于临床筛查多种口腔和全身性疾病,其生物标志物存在于唾液中。
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