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

Carmen Martin-Alonso; Shervin Tabrizi; Kan Xiong; Timothy Blewett; Sainetra Sridhar; Andjela Crnjac; Sahil Patel; Zhenyi An; Ahmet Bekdemir; Douglas Shea; Shih Ting Wang; Sergio Rodriguez-Aponte; Christopher A. Naranjo; Justin Rhoades; Jesse D. Kirkpatrick; Heather E. Fleming; Ava P. Amini; Todd R. Golub; J. Christopher Love; Sangeeta N. Bhatia; Viktor A. Adalsteinsson

doi:10.1126/science.adf2341

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

Carmen Martin-Alonso, Shervin Tabrizi^*, Kan Xiong, Timothy Blewett, Sainetra Sridhar, Andjela Crnjac, Sahil Patel, Zhenyi An, Ahmet Bekdemir, Douglas Shea, Shih Ting Wang, Sergio Rodriguez-Aponte, Christopher A. Naranjo, Justin Rhoades, Jesse D. Kirkpatrick, Heather E. Fleming, Ava P. Amini, Todd R. Golub, J. Christopher Love^*, Sangeeta N. Bhatia^*Viktor A. Adalsteinsson^*

^*Corresponding author for this work

Materials Science and Engineering

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1-10
Number of pages	10
Journal	Science
Volume	383
Issue number	6680
DOIs	https://doi.org/10.1126/science.adf2341
State	Published - Jan 1 2024

Funding

We thank the Koch Institute's Robert A. Swanson (1969) Biotechnology Center for the technical support. Specifically, we thank K. Cormier and R. Bronson from the Koch Institute Histology Core for tissue processing and pathological assessment, respectively, and D. S. Yun from the Nanotechnology Materials Core (RRID:SCR_018674) for assistance on the TEM and cryo–transmission electron microscopy imaging. We thank G. Ha for advice on running Griffin software. We thank S. Cowles, E. Lutz, and K. D. Wittrup for advice and assistance with mammalian expression. We thank G. Gydush for his help setting up the data analysis pipeline leveraged for this work. We thank L. Gaffney for her assistance in designing the graphics for this work. This work was supported in part by a Cancer Center Support (core) grant P30-CA14051 from the National Cancer Institute, a Core Center grant P30-ES002109 from the National Institute of Environmental Health Sciences, the Koch Institute’s Marble Center for Cancer Nanomedicine (S.N.B.), the Gerstner Family Foundation (V.A.A. and T.R.G.), the Koch Institute Frontier Research Program through the Casey and Family Foundation Cancer Research (J.C.L. and S.N.B.) the Virginia and D. K. Ludwig Fund for Cancer Research (S.N.B.), and the Bridge Project, a partnership between the Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center (J.C.L. and V.A.A.). C.M.-A. acknowledges support from a fellowship from La Caixa Foundation (ID 100010434). The fellowship code is LCF/BQ/AA19/11720039. C.M.-A. also acknowledges support from The Ludwig Center Fellowship at MIT's Koch Institute. S.T. acknowledges support from an ASCO Conquer Cancer Foundation Young Investigator Award (2021YIA-5688173400) and a Prostate Cancer Foundation Young Investigator Award (21YOUN20). S.P. acknowledges support from a T32 (T32HL116275). S.N.B. is a Howard Hughes Medical Institute investigator.

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Martin-Alonso, C., Tabrizi, S., Xiong, K., Blewett, T., Sridhar, S., Crnjac, A., Patel, S., An, Z., Bekdemir, A., Shea, D., Wang, S. T., Rodriguez-Aponte, S., Naranjo, C. A., Rhoades, J., Kirkpatrick, J. D., Fleming, H. E., Amini, A. P., Golub, T. R., Love, J. C., ... Adalsteinsson, V. A. (2024). Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies. Science, 383(6680), 1-10. https://doi.org/10.1126/science.adf2341

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title = "Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies",

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.",

author = "Carmen Martin-Alonso and Shervin Tabrizi and Kan Xiong and Timothy Blewett and Sainetra Sridhar and Andjela Crnjac and Sahil Patel and Zhenyi An and Ahmet Bekdemir and Douglas Shea and Wang, {Shih Ting} and Sergio Rodriguez-Aponte and Naranjo, {Christopher A.} and Justin Rhoades and Kirkpatrick, {Jesse D.} and Fleming, {Heather E.} and Amini, {Ava P.} and Golub, {Todd R.} and Love, {J. Christopher} and Bhatia, {Sangeeta N.} and Adalsteinsson, {Viktor A.}",

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Martin-Alonso, C, Tabrizi, S, Xiong, K, Blewett, T, Sridhar, S, Crnjac, A, Patel, S, An, Z, Bekdemir, A, Shea, D, Wang, ST, Rodriguez-Aponte, S, Naranjo, CA, Rhoades, J, Kirkpatrick, JD, Fleming, HE, Amini, AP, Golub, TR, Love, JC, Bhatia, SN & Adalsteinsson, VA 2024, 'Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies', Science, vol. 383, no. 6680, pp. 1-10. https://doi.org/10.1126/science.adf2341

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AU - Martin-Alonso, Carmen

AU - Tabrizi, Shervin

AU - Xiong, Kan

AU - Blewett, Timothy

AU - Sridhar, Sainetra

AU - Crnjac, Andjela

AU - Patel, Sahil

AU - An, Zhenyi

AU - Bekdemir, Ahmet

AU - Shea, Douglas

AU - Wang, Shih Ting

AU - Rodriguez-Aponte, Sergio

AU - Naranjo, Christopher A.

AU - Rhoades, Justin

AU - Kirkpatrick, Jesse D.

AU - Fleming, Heather E.

AU - Amini, Ava P.

AU - Golub, Todd R.

AU - Love, J. Christopher

AU - Bhatia, Sangeeta N.

AU - Adalsteinsson, Viktor A.

PY - 2024/1/1

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

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