When CARMEN met the coronavirus

Say hello to CARMEN: a massively multiplexed, Cas13-based technology for nucleic acid detection, out yesterday in Nature. Its name stands for Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids, and it allows us to test many amplified samples for the presence of many viral sequences by using miniaturized detection reactions that self-organize in a microwell array. Sars-Cov2 included.

“Infectious diseases are some of the greatest threats to human health and global security, yet there is no broadly available molecular test for the vast majority of disease-causing microbes, limiting their diagnosis and surveillance. Of the myriad viral species capable of infecting humans (576 of which had been sequenced, 169 of which had ≥10 published genomes in Oct 2018), only 39 had FDA-approved”, the paper states.

With CARMEN’s help, researchers from the Broad Institute were capable of distinguishing at the 169 human-associated viruses with over ten available genome sequences, claiming high performance and no detectable cross-reactivity. They also developed CARMEN assays for comprehensive influenza subtyping, and assays to identify dozens of HIV drug resistance mutations.

“We’ve been working on this technology for some time, but when COVID-19 emerged in our final round of peer review we rapidly developed a CARMEN panel to distinguish 6 related coronaviruses”, tweeted the corresponding author Cameron Myhrvold.

In short, the team has “demonstrated a broad set of uses for CARMEN-Cas13— differentiating viral sequences at the species, strain, and SNP levels—and the capability to rapidly develop and validate highly multiplexed detection panels. More generally, CARMEN-Cas13 augments CRISPR-based nucleic acid detection technologies by increasing throughput, decreasing reagent and sample consumption per test, and enabling detection over a larger dynamic range”.

The paper ends with a look at the future. “We imagine region- and outbreak-specific detection panels deployed to test thousands of samples from selected populations, including animal vectors, animal reservoirs, or patients presenting with symptoms. […] CARMEN unleashes CRISPR-based diagnostics at scale, a critical step toward routine, comprehensive disease surveillance to improve patient care and public health”.

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