Engineering of a DNA/γPNA Hybrid Nanoreporter for ctDNA Mutation Detection via γPNA Urinalysis.

Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE

Original Publication: Weinheim : WILEY-VCH, [2014]-

Circulating Tumor DNA*/genetics ; Circulating Tumor DNA*/urine ; Circulating Tumor DNA*/blood ; Mutation*/genetics ; Peptide Nucleic Acids*/genetics ; Urinalysis*/methods; Humans ; Biosensing Techniques/methods ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/urine ; Biomarkers, Tumor/blood ; DNA/genetics ; DNA/urine ; Neoplasms/genetics ; Neoplasms/diagnosis ; Neoplasms/urine

Detection of circulating tumor DNA (ctDNA) mutations, which are molecular biomarkers present in bodily fluids of cancer patients, can be applied for tumor diagnosis and prognosis monitoring. However, current profiling of ctDNA mutations relies primarily on polymerase chain reaction (PCR) and DNA sequencing and these techniques require preanalytical processing of blood samples, which are time-consuming, expensive, and tedious procedures that increase the risk of sample contamination. To overcome these limitations, here the engineering of a DNA/γPNA (gamma peptide nucleic acid) hybrid nanoreporter is disclosed for ctDNA biosensing via in situ profiling and recording of tumor-specific DNA mutations. The low tolerance of γPNA to single mismatch in base pairing with DNA allows highly selective recognition and recording of ctDNA mutations in peripheral blood. Owing to their remarkable biostability, the detached γPNA strands triggered by mutant ctDNA will be enriched in kidneys and cleared into urine for urinalysis. It is demonstrated that the nanoreporter has high specificity for ctDNA mutation in peripheral blood, and urinalysis of cleared γPNA can provide valuable information for tumor progression and prognosis evaluation. This work demonstrates the potential of the nanoreporter for urinary monitoring of tumor and patient prognosis through in situ biosensing of ctDNA mutations.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

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NUHSRO/2020/133/Startup/08 National University of Singapore; NUHSRO/2023/008/NUSMed/TCE/LOA National University of Singapore; NUHSRO/2021/034/TRP/09/Nanomedicine National University of Singapore; NUHSRO/2021/044/Kickstart/09/LOA National University of Singapore; MOH-OFIRG23jan-0005 National Medical Research Council; CG21APR1005 National Medical Research Council; MOE-000387-00 Singapore Ministry of Education; NRF-000352-00 National Research Foundation; 22207013 National Natural Science Foundation of China; 81972261 National Natural Science Foundation of China; 82372128 National Natural Science Foundation of China; 31971302 National Natural Science Foundation of China; KYYW202006 Wenzhou Medical University; 2023B1515020071 Natural Science Foundation Distinguished Young Scholars grant of Guangdong Province; China Association for Science and Technology; 2020ZDZX2001 Educational Commission of Guangdong Province of China key Project

Keywords: ctDNA mutation; tumor detection; urinalysis; γPNA

0 (Circulating Tumor DNA)
0 (Peptide Nucleic Acids)
0 (Biomarkers, Tumor)
9007-49-2 (DNA)

Date Created: 20240703 Date Completed: 20240927 Latest Revision: 20240929

20240929

PMC11434236

10.1002/advs.202310225

38958527