| Autor: |
Shervin Tabrizi, Carmen Martin-Alonso, Kan Xiong, Timothy Blewett, Sainetra Sridhar, Zhenyi An, Sahil Patel, Sergio Rodriguez-Aponte, Christopher A. Naranjo, Shih-Ting Wang, Douglas Shea, Todd R. Golub, Sangeeta N. Bhatia, Viktor Adalsteinsson, J. Christopher Love |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
bioRxiv |
| Popis: |
Blood-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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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