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
  • 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.
PMID: 38236959 DOI: 10.1126/science.adf2341
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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