Abstract
Liquid biopsies are enabling minimally invasive monitoring and molecular profiling of diseases across medicine, but their sensitivity remains limited by the scarcity of cell-free DNA (cfDNA) in blood. Here, we report an intravenous priming agent that is given prior to a blood draw to increase the abundance of cfDNA in circulation. Our priming agent consists of nanoparticles that act on the cells responsible for cfDNA clearance to slow down cfDNA uptake. In tumor-bearing mice, this agent increases the recovery of circulating tumor DNA (ctDNA) by up to 60-fold and improves the sensitivity of a ctDNA diagnostic assay from 0% to 75% at low tumor burden. We envision that this priming approach will significantly improve the performance of liquid biopsies across a wide range of clinical applications in oncology and beyond.
Competing Interest Statement
A provisional patent has been filed on this work: PCT/US2022/013769 (ST, CMA, KX, SNB, VAA, JCL). T.R. Golub has advisor roles (paid) at Foundation Medicine, GlaxoSmithKline and Sherlock Biosciences. J.C.L. has interests in Sunflower Therapeutics PBC, Pfizer, Honeycomb Biotechnologies, OneCyte Biotechnologies, QuantumCyte, Amgen, and Repligen. J.C.L.'s interests are reviewed and managed under MIT's policies for potential conflicts of interest. V.A. Adalsteinsson is a member of the scientific advisory boards of AGCT GmbH and Bertis Inc., which were not involved in this study. S.N.B. reports compensation for cofounding, consulting for, and/or board member-ship in Glympse Bio, Satellite Bio, CEND Therapeutics, Catalio Capital, Intergalactic Therapeutics, Port Therapeutics, Vertex Pharmaceuticals, and Moderna, and receives sponsored research funding from Johnson & Johnson, Revitope, and Owlstone. The remaining authors report no conflicts of interest.
Footnotes
↵§ These authors jointly supervised this work.
