Researchers Use CRISPR to Detect HPV and Zika

rbanffy | 236 points

This is huge!

Imagine affordable STD test kits adjacent to the pregnancy testers on the shelves of your local store.

The prostitution story looks a lot different if every encounter can realistically incorporate a predicated broad-spectrum STD test of both parties.

Edit: Usual dating would be a lot less risky as well. Has it become standard practice for couples to both get tested before becoming intimate yet?

newnewpdro | 6 years ago

> Their system uses several CRISPR enzymes, including Cas13 and Csm6, and can be loaded onto a paper strip, making it incredibly easy to use.

Using CRISPR for low cost detection of disease would be a tremendous accomplishment. I wonder if Bill Gates had something like this outcome in mind when he invested into Editas (co-founded by Feng Zhang). It would seem to fit with inexpensive detection approaches he has pursued over the years.

adventured | 6 years ago

We've been hearing about CRISPR for a couple of years now. Any idea what's the approximate ETA to the market of this kind of technology, and are there any other obstacles except for the human trials? (Don't say "ethical questions" because it's a non-issue, there will be always multiple countries who'd ignore that.)

I hope it won't become another graphene, a discovery with enormous potential that would never leave the lab.

vadimberman | 6 years ago

We've collected a number of the various Cas variants into Pinecone if anyone wants to play around with the proteins [1]. In this article they speak of cheap detection, but in some sense those are the natural technological requirements or outcomes of their much more powerful editors (you have to be able to 'see' the results of what you've edited in order to more efficiently edit). In order to better edit, nice readouts were required to be invented.

The Cas systems are 'pointers' or 'cursors' to locate a specific sequence of DNA or RNA - and once you have a good pointer, you can bring to bear all the rest of biology's tricks at that location. Multi-fluorophore systems are great, and gels are easy. It's a super creative effort to utilize those cheap reagents and assays in the context of a creative 'DNA locator' system in order to amplify a single genomic signal to one that is readable by eye, in the field. And that capability makes the debugging of the editors themselves at the more cheap and easy. Our collective 'toolkit' is now becoming complete enough that the creative and combinatorial usage of existing tools will very quickly explode our capabilities.

YC's own Benchling also has the sequences (and is cited in the papers' supplements): https://benchling.com/s/seq-arzpsupZEzGu3ghBDhtv/edit

(Shame on Science Magazine for publishing a supplemental PDF with Benchling links that you cannot click on and sequences that are not copyable (pg 24). It's 2018!: http://science.sciencemag.org/content/sci/suppl/2018/02/14/s... (and Benchling, if your target audience is printing out links, you might want to not use both O and 0 in your UIDs))

Our protein based design software: [1] https://serotiny.bio/pinecone/ (search Cas13, REPAIR)

jfarlow | 6 years ago

These are really great use cases. That said, the article is totally missing the fact that these labs are aggressively developing alternatives to the Cas9 protein to dance around the ongoing CRISPR patent battle...

stupandaus | 6 years ago

How do you get information out of a living cell without destroying it?

Right now observing neuron function within our brains is limited to tools such as magnetic resonance imaging. But molecular recorders, such as the Crispr Camera system demonstrated here. Provide a mechanism for cells to log their own history. With storage space extensible to a petri-sized population of bacteria totalling billions of gigabytes!

I think the vision is more than data storage however. Synthetic biological constructs typically involve complex and precise steps. By encoding the recipe in biology. It ushers in the path for automating the laboratory workflow.

Movie Replayed From Living Cells' DNA Debuts "Molecular Recorder"

https://www.youtube.com/watch?v=gK3dcjBaJyo

indescions_2018 | 6 years ago

Article 1:

Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6

Jonathan S. Gootenberg1,2,3,4,7,, Omar O. Abudayyeh1,2,3,4,5,, Max J. Kellner1, Julia Joung1,2,3,4, James J. Collins1,4,5,6,8, Feng Zhang1,2,3,4,†

Abstract Rapid detection of nucleic acids is integral for clinical diagnostics and biotechnological applications. We recently developed a platform termed SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) that combines isothermal pre-amplification with Cas13 to detect single molecules of RNA or DNA. Through characterization of CRISPR enzymology and application development, we report here four advances integrated into SHERLOCKv2: 1) 4-channel single reaction multiplexing using orthogonal CRISPR enzymes; 2) quantitative measurement of input down to 2 aM; 3) 3.5-fold increase in signal sensitivity by combining Cas13 with Csm6, an auxilary CRISPR-associated enzyme; and 4) lateral flow read-out. SHERLOCKv2 can detect Dengue or Zika virus ssRNA as well as mutations in patient liquid biopsy samples via lateral flow, highlighting its potential as a multiplexable, portable, rapid, and quantitative detection platform of nucleic acids.

http://science.sciencemag.org/content/early/2018/02/14/scien...

Ice_cream_suit | 6 years ago

Article 2:

CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity

Abstract CRISPR-Cas12a (Cpf1) proteins are RNA-guided enzymes that bind and cut DNA as components of bacterial adaptive immune systems. Like CRISPR-Cas9, Cas12a has been harnessed for genome editing based on its ability to generate targeted, double-stranded DNA (dsDNA) breaks. Here we show that RNA-guided DNA binding unleashes indiscriminate single-stranded DNA (ssDNA) cleavage activity by Cas12a that completely degrades ssDNA molecules. We find that target-activated, non-specific ssDNase cleavage is also a property of other type V CRISPR-Cas12 enzymes. By combining Cas12a ssDNase activation with isothermal amplification, we create a method termed DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR), which achieves attomolar sensitivity for DNA detection. DETECTR enables rapid and specific detection of human papillomavirus in patient samples, thereby providing a simple platform for molecular diagnostics.

http://science.sciencemag.org/content/early/2018/02/14/scien...

Ice_cream_suit | 6 years ago

There’s a VC funded company working on this (in the Bay Area) - Mammoth Diagnostics http://www.mammothdiagnostics.com

corwinbad | 6 years ago

Wonder where test blood comes from? For the past year or so, whenever I've donated blood, there's an extra page in the donor materials that explains how a sample of each unit goes to research for developing new tests for Zika. (It's a different Zika research project, I'm sure.)

If you want to help researchers developing new blood tests for emergent diseases (or need another reason to donate blood), it's here and it's easy and free. I think that's cooler than anything I'll ever do with technology.

ken | 6 years ago

Having close to 0 understanding on the subject can't CRISPR theoretically be used to "cut out" the virus DNA to actually cure HPV and other viruses.

qaq | 6 years ago

I'm a deep learning researcher. I wonder if my skills could be useful in the context of CRISPR. It sounds like a terribly promising area

make3 | 6 years ago

I'd wished they'd use <abbr> tags with a tooltip on all those abbreviations... damn.

NKCSS | 6 years ago