Abstract
AbstractBlood-based, or “liquid,” biopsies enable minimally invasive diagnostics but have limits on sensitivity due to scarce cell-free DNA (cfDNA). Improvements to sensitivity have primarily relied on enhancing sequencing technologyex vivo. Here, we sought to augment the level of circulating tumor DNA (ctDNA) detected in a blood draw by attenuating the clearance of cfDNAin vivo. We report a first-in-class intravenous DNA-binding priming agent given 2 hours prior to a blood draw to recover more cfDNA. The DNA-binding antibody minimizes nuclease digestion and organ uptake of cfDNA, decreasing its clearance at 1 hour by over 150-fold. To improve plasma persistence and limit potential immune interactions, we abrogated its Fc-effector function. We found that it protects GC-rich sequences and DNase-hypersensitive sites, which are ordinarily underrepresented in cfDNA. In tumor-bearing mice, priming improved tumor DNA recovery by 19-fold and sensitivity for detecting cancer from 6% to 84%. These results suggest a novel method to enhance the sensitivity of existing DNA-based cancer testing using blood biopsies.
Publisher
Cold Spring Harbor Laboratory
Reference68 articles.
1. Liquid biopsies come of age: towards implementation of circulating tumour DNA
2. Presence of fetal DNA in maternal plasma and serum;The Lancet,1997
3. Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease;Nat Microbiol,2019
4. Circulating Cell-Free DNA Enables Noninvasive Diagnosis of Heart Transplant Rejection
5. M. R. Future , Liquid Biopsy Market Size Worth USD 13.8 Billion by 2030 at 12.4% CAGR - Report by Market Research Future (MRFR). GlobeNewswire News Room (2022), (available at https://www.globenewswire.com/en/news-release/2022/07/25/2485216/0/en/Liquid-Biopsy-Market-Size-Worth-USD-13-8-Billion-by-2030-at-12-4-CAGR-Report-by-Market-Research-Future-MRFR.html).
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