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

Martin-Alonso, Carmen; Tabrizi, Shervin; Xiong, Kan; Blewett, Timothy; Sridhar, Sainetra; Crnjac, Andjela; Patel, Sahil; An, Zhenyi et al. · Science · 2024

basic_science · Level V

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Abstract

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.

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