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

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

  • Science. 2024 Jan 19;383(6680):eadf2341. doi: 10.1126/science.adf2341.
Carmen Martin-Alonso # 1 2 Shervin Tabrizi # 1 3 4 5 Kan Xiong # 3 Timothy Blewett 3 Sainetra Sridhar 3 Andjela Crnjac 3 Sahil Patel 1 3 6 Zhenyi An 3 Ahmet Bekdemir 1 Douglas Shea 3 Shih-Ting Wang 1 Sergio Rodriguez-Aponte 1 7 Christopher A Naranjo 1 Justin Rhoades 3 Jesse D Kirkpatrick 1 2 Heather E Fleming 1 Ava P Amini 8 Todd R Golub 3 5 9 J Christopher Love 1 3 10 Sangeeta N Bhatia 1 2 3 11 12 13 14 Viktor A Adalsteinsson 3
Affiliations

Affiliations

  • 1 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 2 Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 3 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • 4 Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • 5 Harvard Medical School, Boston, MA 02115, USA.
  • 6 Division of Pulmonary and Critical Care, Department of Medicine, Massachusetts General Hospital, Boston, MA 02124, USA.
  • 7 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 8 Microsoft Research, Cambridge, MA 02142, USA.
  • 9 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • 10 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 11 Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 12 Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • 13 Wyss Institute at Harvard University, Boston, MA 02215, USA.
  • 14 Howard Hughes Medical Institute, Cambridge, MA 02138, USA.
  • # Contributed equally.
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.

Figures
Products