A Study in Cas13a

July 30, 2017 2:26 PM

SHERLOCK: a "game changer" for identifying infectious diseases. Even if two targets differ by only a single nucleotide — one has an A and one has a G, for instance — SHERLOCK can tell them apart. It can tell Zika’s genetic material from dengue’s, the DNA in one kind of antibiotic-resistant “superbug” from that in another, and DNA in cancer cells from DNA in healthy cells — even when that DNA is present in quantities equal to a couple of pinches of salt in Lake Superior.

The CRISPR system uses an RNA guide to find targeted section of DNA, allowing us to understand - and add to, or change, or fix - genetic code. Think of it as throwing a child into a grocery store to find candy: they (Cas9) beeline for the lollipops (your chosen string of nucleotides), bring one back to you, and you know this store only has tootsie pops, puh-leeze.

While incredibly powerful and absolutely on the cutting-edge of medical research, CRISPR is not without it's faults and concerns (previously). SHERLOCK might be an exciting step forward.

Specific High sensitivity Enzymatic Reporter, developed by bioengineer James Collins and CRISPR pioneer Feng Zhang uses the Cas13a enzyme to find RNA - rather than DNA - and "cut" extra RNA around the target. It's incredibly sensitive: able to identify viruses in concentrations as low as 2 molecules in a quintillion (that’s a billion billion) . This would make it possible to identify the specific culprit of a disease outbreak with better accuracy and far greater speed. That in turn leads to better diagnosis, lives saved, medications used accurately, and emergency plans crafted swiftly.

One of the major problems in outbreaks is just getting the equipment and knowledge together to make that diagnosis - blood tests aren't cheap, and sometimes the electricity for a fridge is even harder to find than a microscope. SHERLOCK could be as little as 61 cents a test and works even after freeze drying, in a standard test tube or on glass fiber paper, and can run on body heat - making it hardy and inexpensive in the field. To infectious disease researcher Scott Weaver, "It looks like one significant step on the pathway which is the Holy Grail, which is developing point-of-care, or bedside detection, which doesn’t require expensive equipment or even reliable power." The quote of "game changer" comes from Pardis Sabeti, who did groundbreaking work during the last Ebola outbreak.

A video on SHERLOCK: Detecting disease with CRISPR has further information. [Youtube link, has autogenerated captions that are about 95% accurate.]

(With this incredible stretch of an acronym, we must note that our original detective was himself connected to germ research.)

One of the test cases for SHERLOCK was Zika, and Zika - beyond itself as a disease - is a frequent name, like Ebola, we throw around to signify quick and scary and unknown outbreaks. (The Zika virus itself was named in 1947). If you are interested in tracking ongoing outbreaks, the Emerging Infectious Diseases journal is free from the CDC, Disease Outbreak News from the WHO, and Healthmap provides an interactive map of outbreaks on the small and large scale from news sources around the globe.

Some disease outbreaks require advanced techniques like SHERLOCK. Others can be identified with classic techniques, and do not need advanced technology to stop them - just the will to do so. Yemen is currently suffering a cholera outbreak the UN is calling the "worst in the world". UNICEF and WHO are working with local agencies to save lives and would welcome your assistance.

posted by hapaxes.legomenon (5 comments total)

but the key word is ‘promising’: It’s going to be a long walk from hopeful to clinically useful, and there is a lot to do to demonstrate practicality.”
posted by porpoise at 2:49 PM on July 30, 2017

This immediately makes me think of something that I've heard cancer researchers mention a bunch of times: Because cancer cell genomes can be so varied even within a single tumor, it's often hard to tell whether a particular mutation is present in tiny amounts or whether the sequencer is making an error. I'd be interested to know whether this would help with that problem; it sounds like it might.
posted by clawsoon at 3:37 PM on July 30, 2017 [1 favorite]

Yeah, team Doudna (the Berkeley group still in patent disputes with Zhang & colleagues) has one of these RNA-guided RNA endonuclease based diagnostics in the works too, but just published and patented, no fancy names for shopping press pieces about the test as far as I know. Theirs is a c2c2 enzyme. I hadn't heard of Cas13a, so I looked it up, and evidently it's the same protein, different name. So... Berkeley vs Broad CRISPR wars FOREVAR.

I'm sorta jaded when it comes to PR around inexpensive bedside diagnostics that require no cold chain and can be used in the field because there's just not enough money to be made in developing and selling them. (Yay, capitalism-driven healthcare innovation!) You get dozens or hundreds of these stories a year, but very few of the technologies make it out of academia, much less into widespread use. It's sad. But I bet some kind of test based on CRISPR-guided RNA cleavage will get developed, probably starting with (expensive) viral screening.
posted by deludingmyself at 6:05 PM on July 30, 2017 [9 favorites]

So... Berkeley vs Broad CRISPR wars FOREVAR.

Naw, 17 years. VS the ongoing extension of legal protection of intellectual "property" of copyright extensions.

Whomever wants to "win" the war can be the 1st to say "We want to protect the rights and we'd allow $0 fees to use our rights. Because we are humanitarians and all that rubbish." Throw in some insults in the PR release and bam! its presidential level gravitas.
posted by rough ashlar at 2:49 AM on July 31, 2017 [1 favorite]

Naw, 17 years.

Well sure, but that assumes Zhang and Doudna stop patenting new CRISPR-related technologies. Which... is not happening.
posted by deludingmyself at 5:54 PM on July 31, 2017 [2 favorites]