Programmable enzyme–enabled ultra-sensitive liquid biopsy for early detection of tumor MRD

Title : Programmable enzyme–enabled ultra-sensitive liquid biopsy for early detection of tumor MRD

Abstract:

Minimal residual disease (MRD) can persist in cancer patients even after potential cure, resulting in cancer recurrence and contributing to the low five-year survival rate of cancer patients. Currently, circulating tumor DNA (ctDNA) is the preferred biomarker for MRD detection. However, due to the extremely similar nucleic acid sequences, wild type nucleic acid existing in body fluids in large quantities poses a big challenge to the highly sensitive detection of ctDNA.

We developed a new ultra-sensitive ctDNA detection method using programmable nuclease and dubbed it PASEA (Programmable Enzyme-Assisted Selective Exponential Amplification), which, in the process of nucleic acid amplification, wildtype nucleic acid was specifically cleaved by programmable endonuclease, including Argonaute and CRISPR-Cas systems, to achieve the specific exponential enrichment of ctDNA, so that the detection sensitivity could be lower than 0.01% MAF. We conducted a clinical evaluation of PASEA for tumor efficacy monitoring and MRD detection through follow-up monitoring of patients who received chemotherapy and surgery. Our analysis revealed that PASEA is a powerful tool for predicting cancer recurrence and guiding personalized treatment, offering significant clinical benefits. We also observed that the detection rate of ctDNA in pancreatic cancer was closely linked to treatment status, efficacy and metastatic site.

Biography:

Jinzhao Song is a Professor at the Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang Cancer Hospital. Prior to this role, he served as a Research Assistant Professor at the University of Pennsylvania, School of Engineering and Applied Science. Dr. Song received his Ph.D. from the Institute of Chemistry, Chinese Academy of Sciences (ICCAS). With over 15 years of experience, he has focused on developing next generation molecular diagnostic systems based on isothermal nucleic acid amplification; microfluidic chip that utilize smartphones for detection, analysis, result recording and sharing; and programmable enzymes such as Argonaute and CRISPR-Cas proteins. He has co-authored 51 peer-reviewed papers with H-index 23, 15 of which he was the lead author, and was named as co-inventor in 9 granted patents and 10 patent applications. Dr. Song is a recipient of the NIH K01 Research Scientist Development Award, as well as a PI/co-PI of an R21 NIH grant and two venture incubation programs. His contributions to the field of molecular diagnostics earned him the AACC's "2019 Young Investigator Award for Outstanding Research in Personalized Medicine." Additionally, Dr. Song founded EzDx Technology Inc., an enterprise dedicated to the commercialization and widespread adoption of these cutting-edge diagnostic tools, thereby setting a new standard in healthcare diagnostics and personalized medicine.