Portable crispr-based diagnostics

You have full access to this article via your institution. Download PDF A new molecular diagnostics startup formed around CRISPR and synthetic biology technologies has raised $35 million in

a series A, taking its total funding to $49 million since its launch in March. The company, called Sherlock Biosciences, aims to develop affordable, instrument-free diagnostic tests for use

in oncology and infectious diseases as well as industrial and agricultural applications. It is developing two platforms: SHERLOCK, which uses CRISPR to detect genetic fingerprints that

signal the presence of pathogens; and INSPECTR, a synthetic biology–based tool. SHERLOCK, which stands for specific high-sensitivity enzymatic reporter unlocking, uses the RNA-targeting

Cas13 enzyme to identify specific genetic targets. Cas13 also cleaves nearby RNAs, a ‘collateral’ feature useful for amplifying a reporter signal in a diagnostic test. The signal can be read

with a simple paper strip or as an electrochemical readout using a mobile phone. INSPECTR, short for internal splint-pairing expression cassette translation reaction, is a DNA

hybridization–based sensor that detects DNA or RNA with single-base-pair sensitivity coupled with a bioluminescent signal, which allows visualization at room temperature. Cofounders Feng

Zhang from the Broad Institute and James Collins from MIT and Harvard’s Wyss Institute first published on SHERLOCK in 2017, demonstrating it could detect low levels of Zika virus, as well as

the presence of pathogenic bacteria. Their team subsequently improved detection and signal sensitivity by combining Cas13 with other enzymes. Sherlock joins 2018 startup Mammoth Biosciences

in the race to develop CRISPR diagnostics. Mammoth initially used a combination of Cas12 and Cas13 to simultaneously detect DNA and RNA, later adding Cas14, discovered by cofounders

Jennifer Doudna and Lucas Harrington. Researchers at the University of California, San Francisco, and the Chan Zuckerberg Biohub also recently disclosed FLASH (finding low abundance

sequences by hybridization), a CRISPR–Cas9 diagnostic for identifying drug-resistant microbes. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Portable

CRISPR-based diagnostics. _Nat Biotechnol_ 37, 832 (2019). https://doi.org/10.1038/s41587-019-0220-1 Download citation * Published: 02 August 2019 * Issue Date: August 2019 * DOI:

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