Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies

• 成果类型: Article
• 署名作者: Martin-Alonso, Carmen; Tabrizi, Shervin; Xiong, Kan; Blewett, Timothy; Sridhar, Sainetra; Crnjac, Andjela; Patel, Sahil; An, Zhenyi; Bekdemir, Ahmet; Shea, Douglas; Wang, Shih-Ting; Rodriguez-Aponte, Sergio; Naranjo, Christopher A.; Rhoades, Justin; Kirkpatrick, Jesse D.; Fleming, Heather E.; Amini, Ava P.; Golub, Todd R.; Love, J. Christopher; Bhatia, Sangeeta N.; Adalsteinsson, Viktor A.
• 署名单位: Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Massachusetts Institute of Technology (MIT); Microsoft; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Howard Hughes Medical Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11020
• DOI: 10.1126/science.adf2341
• 发表日期: 2024-01-19
• 关键词: groundwater; irrigation; INDIA

摘要

Liquid biopsies enable early detection and monitoring of diseases such as cancer, but their sensitivity remains limited by the scarcity of analytes such as cell-free DNA (cfDNA) in blood. Improvements to sensitivity have primarily relied on enhancing sequencing technology ex vivo. We sought to transiently augment the level of circulating tumor DNA (ctDNA) in a blood draw by attenuating its clearance in vivo. We report two intravenous priming agents given 1 to 2 hours before a blood draw to recover more ctDNA. Our priming agents consist of nanoparticles that act on the cells responsible for cfDNA clearance and DNA-binding antibodies that protect cfDNA. In tumor-bearing mice, they greatly increase the recovery of ctDNA and improve the sensitivity for detecting small tumors.