Yang Sha, Zhan Xinyu, Tang Xiaoqi, Zhao Shuang, Yu Lianyu, Gao Mingxuan, Luo Dan, Wang Yunxia, Chang Kai, Chen Ming
Department of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba District, Chongqing, 400038, China.
Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, 14853-5701, USA.
Bioact Mater. 2021 Sep 11;10:68-78. doi: 10.1016/j.bioactmat.2021.09.007. eCollection 2022 Apr.
Circulating tumor DNA (ctDNA) is a critical biomarker not only important for the early detection of tumors but also invaluable for personalized treatments. Currently ctDNA detection relies on sequencing. Here, a platform termed three-dimensionalcoded interlocked DNA rings (3D-coded ID rings) was created for multiplexed ctDNA identification. The ID rings provide a ctDNA recognition ring that is physically interlocked with a reporter ring. The specific binding of ctDNA to the recognition ring initiates target-responsive cutting via a restriction endonuclease; the cutting then triggers rolling circle amplification on the reporter ring. The signals are further integrated with internal 3D codes for multiplexed readouts. ctDNAs from non-invasive clinical specimens including plasma, feces, and urine were detected and validated at a sensitivity much higher than those obtained through sequencing. This 3D-coded ID ring platform can detect any multiple DNA fragments simultaneously without sequencing. We envision that our platform will facilitate the implementation of future personalized/precision medicine.
循环肿瘤DNA（ctDNA）是一种关键的生物标志物，不仅对肿瘤的早期检测至关重要，而且对个性化治疗也具有不可估量的价值。目前，ctDNA检测依赖于测序。在此，创建了一个名为三维编码互锁DNA环（3D编码ID环）的平台用于多重ctDNA鉴定。ID环提供了一个与报告环物理互锁的ctDNA识别环。ctDNA与识别环的特异性结合通过限制性内切酶启动靶标响应切割；切割随后触发报告环上的滚环扩增。信号进一步与内部3D编码整合以进行多重读数。来自包括血浆、粪便和尿液在内的非侵入性临床标本中的ctDNA被检测并验证，其灵敏度远高于通过测序获得的灵敏度。这个3D编码ID环平台无需测序就能同时检测任何多个DNA片段。我们设想我们的平台将促进未来个性化/精准医学的实施。
