Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies
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nihms-2028973.pdf
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Accepted version
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1.35 MB
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Author(s) • • • • • • • • •
Martin-Alonso, Carmen
Tabrizi, Shervin
Xiong, Kan
Blewett, Timothy
Sridhar, Sainetra
Crnjac, Andjela
Patel, Sahil
An, Zhenyi
Bekdemir, Ahmet
Shea, Douglas
Date Issued
January 19, 2024
Journal
Science
Publisher
American Association for the Advancement of Science
Citation
Carmen Martin-Alonso et al. ,Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies.Science 383, eadf2341 (2024).
Version
Author's final manuscript
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Harvard-MIT Program in Health Sciences and Technology
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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Creative Commons Attribution-Noncommercial-ShareAlike
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DOI of Published Version
https://doi.org/10.1126/science.adf2341