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

作者：Carmen Martin-Alonso, Shervin Tabrizi, Kan Xiong, Timothy Blewett, Sainetra Sridhar, Andjela Crnjac, Sahil Patel, Zhenyi An, Ahmet Bekdemir, Douglas Shea, Shih‐Ting Wang, Sergio A. Rodriguez‐Aponte, Christopher A. Naranjo, Justin Rhoades, Jesse D. Kirkpatrick, Heather E. Fleming, Ava P. Amini, Todd R. Golub, John Christopher Love, Sangeeta N. Bhatia, Viktor A. Adalsteinsson · 发表于：Science · 年份：2024 · DOI：10.1126/science.adf2341 · 被引用次数：164 · 研究领域：Cancer Genomics and Diagnostics、Single-cell and spatial transcriptomics、CRISPR and Genetic Engineering

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.