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 t...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.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81972027,82030066,82122042,81430053).
文摘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.