Organoids & CRISPR in the toolbox of virologists

Human gut organoids infected with SARS-CoV-2 (Credit: Joep Beumer/Hubrecht Institute)

“Virologists have infected millions of miniature organs with SARS-CoV-2, to learn how the virus wreaks havoc and how to stop it,” writes Smriti Mallapaty in the latest issue of Nature. In one study, published in Science Immunology in 2020, researchers used CRISPR in gut organoids to identify two proteins (TMPRSS2 and TMPRSS4) that facilitate the virus entry into human cells, together with the ACE2 receptor. “Other labs are knocking out ACE2 entirely, to see whether the virus can still get in”. Here the full text of the news feature.

CRISPR antivirals, where are we now?

CRISPR-based diagnostic tests for Sars-Cov2 are coming, as you probably know. But what about CRISPR-based antiviral therapy? It would seem a natural outcome for a technology inspired by the way many bacteria fight their viruses. Indeed this kind of research is being pursued in a handful of labs, using a CRISPR enzyme targeting RNA instead of DNA.

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CRISPR-based Covid tests: what’s going on?

Doudna’s creature (Mammoth Biosciences) and Zhang’s company (Sherlock Biosciences) are developing CRISPR-based coronavirus tests similar to a home pregnancy test: portable, cheap, fast, and simple. Both will be easily adapted to detect any new emerging virus. Both received emergency use authorizations in the US in the fall of 2020 and hope to enter the market by the end of 2021. According to this piece by Walter Isaacson, competition is hot but all the intellectual property questions have been put aside for common good.

CRISPR milestone: FDA approves first diagnostic test

May 7th 2020 will be remembered as a good day for CRISPR. Yesterday the first CRISPR/Cas-based test received Emergency Use Authorization from the U.S. Food and Drug Administration. The Sherlock SARS-CoV2 kit works by programming a CRISPR enzyme to detect the coronavirus genetic signature, providing results in about one hour. Quickly and cheaply indeed, as the materials for one test cost about $6.

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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.

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CRISPR targeting COVID-19

Alexandra East-Seletsky graphic

Hopefully, CRISPR-based diagnostics will make an early debut amid COVID-19 outbreak. But what about a CRISPR prophylactic strategy to combat coronaviruses? The proof of concept is here, in bioRxiv, but it will be deployed in the next pandemic if we are lucky. It’s called PAC-MAN, like the videogame, stands for Prophylactic Antiviral CRISPR in huMAN cells, and comes from the Stanley Qi Lab.

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