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Title:
CRISPR-Cas-amplified urine biomarkers for multiplexed and portable cancer diagnostics | bioRxiv
Description:
Synthetic biomarkers, exogenous probes that generate molecular reporters, represent an emerging paradigm in precision diagnostics with applications across infectious and noncommunicable diseases. In order to achieve their promise, these methods reply on multiplexing strategies to provide tools that are both sensitive and specific. However, the field of synthetic biomarkers has not benefited from molecular strategies such as DNA-barcoding due to the susceptibility of nucleic acids in vivo . Herein, we exploit chemically-stabilized DNAs to tag synthetic biomarkers and produce diagnostic signals via CRISPR nucleases. Our strategy capitalizes on disease-associated, protease-activated release of nucleic acid barcodes and polymerase-amplification-free, CRISPR-Cas-mediated barcode detection in unprocessed biofluids. In murine cancer models, we show that the DNA-encoded urine biomarkers can noninvasively detect and monitor disease progression, and demonstrate that nuclease amplification can be harnessed to convert the readout to a point-of-care tool. This technique combines specificity with ease of use to offer a new platform to study human disease and guide therapeutic decisions. ### Competing Interest Statement S.N.B., L.H. are listed as inventors on patent applications related to the content of this work. S.N.B. holds equity in Glympse Bio and Impilo Therapeutics, is a director at Vertex, consults for Cristal, Maverick, and Moderna, and receives sponsored research funding from Johnson & Johnson.
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Keywords {🔍}
biology, biomarkers, cancer, synthetic, medrxiv, subject, reviews, clinical, preprint, molecular, biorxiv, university, trials, epidemiology, content, search, results, urine, diagnostics, pdf, applications, strategies, tools, nucleic, disease, snb, research, johnson, copyright, institute, technology, bioengineering, context, genetics, microbiology, papers, submitted, cookies, skip, main, homesubmitfaqblogalerts, rssresourcesaboutchannels, keyword, advanced, follow, crisprcasamplified, multiplexed, portable, liangliang, hao,
Topics {✒️}
crispr-cas-mediated barcode detection epidemiology subject categories clinical trials dna-encoded urine biomarkers generate molecular reporters exploit chemically-stabilized dnas murine cancer models genetics microbiology biorxiv subject category molecular strategies tag synthetic biomarkers epidemiology papers reviews provide tools author/funder keyword advanced search health-related information dna-barcoding due synthetic biomarkers produce diagnostic signals protease-activated release technique combines specificity guide therapeutic decisions competing interest statement generous financial support chan zuckerberg initiative imperial college london vrije universiteit amsterdam articles animal behavior nucleic acid barcodes polymerase-amplification-free monitor disease progression study human disease patent applications related context crispr nucleases precision diagnostics nucleic acids nuclease amplification results follow chayanon ngambenjawong exogenous probes emerging paradigm noncommunicable diseases methods reply multiplexing strategies strategy capitalizes unprocessed biofluids noninvasively detect
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