Priming agents improve in vivo recovery of cell-free DNA and enhance the sensitivity of liquid biopsies

Liquid biopsies are enabling 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. Here, 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 first-in-class intravenous priming agents given 1-2 hours prior to 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 increase the recovery of ctDNA up to 19- to 60-fold and improve the sensitivity for detecting small tumors from 75%. We envision that priming agents could enhance the performance of liquid biopsies in oncology and beyond.