Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies.
Carmen Martin-AlonsoShervin TabriziKan XiongTimothy BlewettSainetra SridharAndjela CrnjacSahil PatelZhenyi AnAhmet BekdemirDouglas SheaShih-Ting WangSergio A Rodriguez-AponteChristopher A NaranjoJustin RhoadesJesse D KirkpatrickSangeeta N BhatiaAva P SoleimanyTodd R GolubJohn Christopher LoveSangeeta N BhatiaViktor A AdalsteinssonPublished in: Science (New York, N.Y.) (2024)
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.
Keyphrases
- circulating tumor
- circulating tumor cells
- cell free
- dna binding
- induced apoptosis
- transcription factor
- ionic liquid
- papillary thyroid
- cell cycle arrest
- ultrasound guided
- high dose
- single cell
- adipose tissue
- cell death
- skeletal muscle
- cell proliferation
- signaling pathway
- metabolic syndrome
- wild type
- childhood cancer
- nucleic acid