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Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies.
Martin-Alonso, Carmen; Tabrizi, Shervin; Xiong, Kan; Blewett, Timothy; Sridhar, Sainetra; Crnjac, Andjela; Patel, Sahil; An, Zhenyi; Bekdemir, Ahmet; Shea, Douglas; Wang, Shih-Ting; Rodriguez-Aponte, Sergio; Naranjo, Christopher A; Rhoades, Justin; Kirkpatrick, Jesse D; Fleming, Heather E; Amini, Ava P; Golub, Todd R; Love, J Christopher; Bhatia, Sangeeta N; Adalsteinsson, Viktor A.
Afiliação
  • Martin-Alonso C; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Tabrizi S; Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Xiong K; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Blewett T; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Sridhar S; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Crnjac A; Harvard Medical School, Boston, MA 02115, USA.
  • Patel S; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • An Z; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Bekdemir A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Shea D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wang ST; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Rodriguez-Aponte S; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Naranjo CA; Division of Pulmonary and Critical Care, Department of Medicine, Massachusetts General Hospital, Boston, MA 02124, USA.
  • Rhoades J; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Kirkpatrick JD; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Fleming HE; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Amini AP; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Golub TR; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Love JC; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Bhatia SN; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Adalsteinsson VA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Science ; 383(6680): eadf2341, 2024 01 19.
Article em En | MEDLINE | ID: mdl-38236959
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácidos Nucleicos Livres / Neoplasias Tipo de estudo: Diagnostic_studies / Screening_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácidos Nucleicos Livres / Neoplasias Tipo de estudo: Diagnostic_studies / Screening_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article