Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies
- 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 ,
- J. C. Love ,
- Sangeeta N. Bhatia ,
- V. Adalsteinsson
Science | , Vol 383: pp. eadf2341-eadf2341
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.