A multiplexed circulating tumor DNA detection platform engineered from 3D-coded interlocked DNA rings

• Published in: Bioactive materials Vol. 10; pp. 68 - 78
• Main Authors: Yang, Sha, Zhan, Xinyu, Tang, Xiaoqi, Zhao, Shuang, Yu, Lianyu, Gao, Mingxuan, Luo, Dan, Wang, Yunxia, Chang, Kai, Chen, Ming
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.04.2022; KeAi Publishing; KeAi Communications Co., Ltd
• Subjects: 3D-coded ID rings; Circulating tumor DNA; Colorectal cancer; Multiplexed detection; 3D-coded ID rings; Multiplexed detection; Circulating tumor DNA; Colorectal cancer
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2021.09.007

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-dimensional-coded 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. A platform termed three-dimensional-coded interlocked DNA rings (3D-coded ID rings) was engineered for multiplexed ctDNA identification. [Display omitted] •A platform termed 3D-coded ID rings was created for multiplexed ctDNA detection.•This platform was integrated with two schemes: the ID ring scheme and the 3D-coded scheme.•The platform could achieve multiplexed detection with detection limit of 500 copies per million in non-invasive specimens.