生物标志物对于恶性肿瘤等疾病的深入了解、精准诊断、靶向治疗和预后评定至关重要。不过，由于人体内的生物标志物微乎其微，而且缺乏识别疾病特异性稀有分子的灵敏方法，发现新的生物标志物仍然存在巨大困难，尤其癌症早期阶段。
2023年9月14日，英国《自然》旗下《自然化学》在线发表复旦大学胡沁沁①(现上海交通大学)、佟宗轩①、阿依木克地斯·亚力孔①、葛丽萍①、时强、杜鑫雨、王璞、刘西禹、詹屋强、高霞、孙迪、傅彤、叶丹、樊春海院士(上海交通大学)、刘杰、钟芸诗📧、江一舟📧、顾宏周📧(现上海交通大学)等学者的研究报告，开发出一种亲合催化分子识别（MORAC）新技术，能够有效发现丰度极低的新型生物标志物，有望对癌症以及其他疾病的筛查、诊断和随访发挥重要作用。
MORAC依赖于一类脱氧核糖核酸（DNA）酶，每种DNA酶可在特异性感应复杂系统时切割嵌入其DNA链的唯一核糖核酸（RNA）连接，而无需事先了解该系统的分子组成。
该研究证实，通过催化将信号扩增可确保DNA酶用于探测靶点时的高灵敏度；同时，简单的RNA到DNA突变可以关闭其RNA切割能力，并将其转变为单纯亲合工具用于靶点重组融合。
该研究利用MORAC发现了以前未知的低丰度候选生物标志物，具有明确的临床价值，包括三阴性乳腺癌的载脂蛋白APOL6和结肠癌前息肉的丝氨酰转运核糖核酸合成酶SARS1，有望对乳腺癌和结肠癌等疾病的筛查、诊断和随访发挥重要作用。
基于DNA酶的MORAC技术用于从病变标本中发现潜在生物标志物利用MORAC从乳腺癌细胞系确定APOL6为候选生物标志物利用MORAC从结肠癌前息肉组织确定SARS1为候选生物标志物结肠低分级和高分级上皮内瘤变SARS1增加，而结肠癌未增加Nat Chem. 2023 Sep 14. IF: 21.8DNAzyme-based faithful probing and pulldown to identify candidate biomarkers of low abundance.Qinqin Hu, Zongxuan Tong, Ayimukedisi Yalikong, Li-Ping Ge, Qiang Shi, Xinyu Du, Pu Wang, Xi-Yu Liu, Wuqiang Zhan, Xia Gao, Di Sun, Tong Fu, Dan Ye, Chunhai Fan, Jie Liu, Yun-Shi Zhong, Yi-Zhou Jiang, Hongzhou Gu.Fudan University Shanghai Cancer Center, Shanghai Stomatological Hospital, Zhongshan Hospital, Fudan University, Shanghai, China; School of Chemistry and Chemical Engineering, School of Global Health, Shanghai Jiao Tong University, Shanghai, China; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Jiao Tong University, Shanghai, China; Zhangjiang Laboratory, Shanghai, China; Huashan Hospital, Fudan University, Shanghai, China.Biomarker discovery is essential for the understanding, diagnosis, targeted therapy and prognosis assessment of malignant diseases. However, it remains a huge challenge due to the lack of sensitive methods to identify disease-specific rare molecules. Here we present MORAC, molecular recognition based on affinity and catalysis, which enables the effective identification of candidate biomarkers with low abundance. MORAC relies on a class of DNAzymes, each cleaving a sole RNA linkage embedded in their DNA chain upon specifically sensing a complex system with no prior knowledge of the system's molecular content. We show that signal amplification from catalysis ensures the DNAzymes high sensitivity (for target probing); meanwhile, a simple RNA-to-DNA mutation can shut down their RNA cleavage ability and turn them into a pure affinity tool (for target pulldown). Using MORAC, we identify previously unknown, low-abundance candidate biomarkers with clear clinical value, including apolipoprotein L6 in breast cancer and seryl-tRNA synthetase 1 in polyps preceding colon cancer.DOI: 10.1038/s41557-023-01328-5
本站仅提供存储服务，所有内容均由用户发布，如发现有害或侵权内容，请
点击举报。
