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

Author:

Martin-Alonso Carmen12ORCID,Tabrizi Shervin1345ORCID,Xiong Kan3ORCID,Blewett Timothy3,Sridhar Sainetra3ORCID,Crnjac Andjela3ORCID,Patel Sahil136ORCID,An Zhenyi3,Bekdemir Ahmet1,Shea Douglas3ORCID,Wang Shih-Ting1ORCID,Rodriguez-Aponte Sergio17ORCID,Naranjo Christopher A.1,Rhoades Justin3ORCID,Kirkpatrick Jesse D.12ORCID,Fleming Heather E.1ORCID,Amini Ava P.8ORCID,Golub Todd R.359ORCID,Love J. Christopher1310ORCID,Bhatia Sangeeta N.1231112ORCID,Adalsteinsson Viktor A.3ORCID

Affiliation:

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.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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