RT Journal Article
SR Electronic
T1 A nanoparticle priming agent reduces cellular uptake of cell-free DNA and enhances the sensitivity of liquid biopsies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.01.13.524003
DO 10.1101/2023.01.13.524003
A1 Carmen Martin-Alonso
A1 Shervin Tabrizi
A1 Kan Xiong
A1 Timothy Blewett
A1 Sahil Patel
A1 Zhenyi An
A1 Sainetra Sridhar
A1 Ahmet Bekdemir
A1 Douglas Shea
A1 Ava P. Amini
A1 Shih-Ting Wang
A1 Jesse Kirkpatrick
A1 Justin Rhoades
A1 Todd R. Golub
A1 J. Christopher Love
A1 Viktor A. Adalsteinsson
A1 Sangeeta N. Bhatia
YR 2023
UL http://biorxiv.org/content/early/2023/01/14/2023.01.13.524003.abstract
AB 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 StatementA 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.