
Researchers Use CRISPR to Detect HPV and Zika - rbanffy
https://www.engadget.com/2018/02/15/crispr-detect-hpv-and-zika/
======
newnewpdro
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?

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

Disease spread is such a drop-in-the-bucket among the (moral, ethical,
personal, societal) issues surrounding prostitution that I have a hard time
understanding how this news changes the story.

It's great news; but prostitution is an issue that deserves a lot of time and
discussion -- and likely the solutions will be social, not technological.

~~~
DoreenMichele
Given that heterosexual dates are typically paid for by men and husbands
typically make a lot more than their wives, it could be argued that the
overwhelming majority of heterosexual sex is some form of prostitution. Yet
when I criticize dating on that basis, I get called a nutter.

When men and women have some kind of parity where women are not routinely
considering their bottom line when deciding how much crap to take in an
unhappy relationship, then you can talk to me about the immorality of
prostitution. Until then, wow, what a way to put on blinders as to how the
vast majority of relationships work.

~~~
root_axis
That's an absurd comparison. Most women have sex with their husbands willingly
because they like sex and they like their husband. Prostitution is a quid pro
quo business arrangement. Of course, sugar-daddy type relationships _do_
exist, but they are not the norm. Consider the example of your own parents. Is
your mother akin to a prostitute because she had sex with your dad at the same
time that he may have been providing for her material needs?

~~~
DoreenMichele
_Is your mother akin to a prostitute because she had sex with your dad at the
same time that he may have been providing for her material needs?_

This is a dirty tactic. It is not good faith engagement.

I'm a woman who has a strict _no dating_ policy, by which I mean that I don't
establish romantic relationships based on some man spending money on me. I am
entirely satisfied with the positive impact that policy has had on my life.

From what I have read and heard over the years, no, most women don't have sex
with their husband because they like him. There are relationships like that,
certainly. But the financial factor pretty clearly poisons quite a lot of
relationships.

I often think this should be the foundational argument as to why men should be
more invested in helping make gender parity happen. If you are a well paid man
and tired of feeling like women only date you for your money, fostering a
world in which women have money of their own on pat with men is the single
best antidote to your dating problem.

As just one supporting citation, this article talks about the fact that pro
athletes frequently marry their high school sweetheart because you can't trust
that women who met you after you struck it rich really like you. They may just
be there for the money. (The article does not use those exact words, but that
is the gist of it.)

[https://www.si.com/vault/2009/03/23/105789480/how-and-why-
at...](https://www.si.com/vault/2009/03/23/105789480/how-and-why-athletes-go-
broke)

There are also rap song lyrics about how poor men from the hood can't get a
date, but once they strike it rich "it's a puss buffet."

I have read articles where, for example, a guy lost his job and his wife quit
having sex with him. He stated that he learned his paycheck was the most
attractive thing about him. A friend of a friend lost his well paid job and
his wife left him because "it wasn't any fun anymore."

The term _gold digging whore_ is a gendered term. It exists because men
typically make a lot more than women and a lot of women are primarily
interested in finding someone to pay their bills. This is compounded by the
difficulties women face in pursuing serious careers of their own.

While I was homeless, no one wanted to open doors for me career wise. But lots
of men wanted to offer me money or a place to stay if I would sleep with them.

In my experience, this problem runs shockingly deep. If your romantic
relationships are unaffected by it, count yourself lucky.

~~~
root_axis
> _This is a dirty tactic. It is not good faith engagement._

It's not a dirty tactic, it's an analogy meant to snap the reader out of
reductive thinking. It's easy to throw out these kind of generalizations when
you reduce people to animals, but when you're forced to consider individuals
from a human perspective (like in the case of your own mother) suddenly there
is a wave of humanizing rationalizations to explain why characterizing
marriage as glorified prostitution doesn't really apply in grandma's case.

> _most women don 't have sex with their husband because they like him_

Neither one of us can prove what is in the head of most women when they get
into bed with their husbands, but it seems absurd to _generally_ ascribe a
financial motivation for married sex-life. Women like sex too, some more than
others, it doesn't make a woman a whore if she also enjoys financial support
(and you know, all the other qualities that people care about in lasting
relationships.

> _If you are a well paid man and tired of feeling like women only date you
> for your money, fostering a world in which women have money of their own on
> pat with men is the single best antidote to your dating problem_

This simply isn't a problem for the vast majority of people. Most eligible
bachelors do not make enough money to such an effect where they have to be
worried about goldiggers beyond the normal common-sense signs.

> _As just one supporting citation, this article talks about the fact that pro
> athletes frequently marry their high school sweetheart because you can 't
> trust that women who met you after you struck it rich really like you_

Individuals with multimillion dollar salaries are clear outliers that have to
contend with the impact of their wealth in _every_ personal relationship,
trying to generalize that example to the general population doesn't make
sense.

> _There are also rap song lyrics about how poor men from the hood can 't get
> a date, but once they strike it rich "it's a puss buffet."_

Once again, if you become rich and famous you are an outlier that is pointless
to apply as a general rule. Also, as someone from the hood, where almost every
individual is poor, I promise you that there are LOTS of dates and LOTS of
sex, even for broke guys, the most common distinction between guys getting
dates and those who are not is confidence, looks, and a sense of humor.

> _a guy lost his job and his wife quit having sex with him_

Yeah... nobody is saying that doesn't happen, but that is obviously not a
common occurrence as any married man who has been unemployed can attest to.

> _While I was homeless, no one wanted to open doors for me career wise. But
> lots of men wanted to offer me money or a place to stay if I would sleep
> with them._

The fact that men have solicited you has means nothing with regard to the
nature of sex within marriage.

~~~
dang
Please don't "snap the reader out of reductive thinking" by using personally
abrasive rhetoric on HN.

Thoughtful conversation works better on a peer basis anyhow, not when one
party presumes higher consciousness than the other.

~~~
root_axis
Dang, I have the greatest respect for your efforts to improve discourse on the
site, but I have to disagree that this is "personally abrasive rhetoric"; the
personal aspect is a critical component of the logic within my argument, it is
precisely the fact that when we consider our own loved ones in the context of
the GP's stated position, it becomes clear that the reasoning is not
consistent (because we offer our loved ones a more humanizing outlook when
considering the nature of their circumstances rather than describing our
mothers and sisters as prostitutes). On a personal note, I am a little
surprised that my comment has been flagged as "personally abrasive" but the
GP's rhetoric suggesting that married women in general can be likened to
prostitutes is not similarly flagged as inflammatory. I am not asking for
permission to continue debating this thread, I am only asking that you
consider the nuance and context of my reply before judging it as abrasive.
Thanks for your hard work.

------
adventured
> 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.

------
vadimberman
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.

~~~
jessriedel
CRISPR cancer therapies are in clinical trials in China, with American and
Europeans trials starting in the next year.

[https://www.technologyreview.com/s/609722/crispr-
in-2018-com...](https://www.technologyreview.com/s/609722/crispr-
in-2018-coming-to-a-human-near-you/)

[https://www.wired.com/story/crispr-therapeutics-plans-its-
fi...](https://www.wired.com/story/crispr-therapeutics-plans-its-first-
clinical-trial-for-genetic-disease/)

[https://www.wsj.com/articles/china-unhampered-by-rules-
races...](https://www.wsj.com/articles/china-unhampered-by-rules-races-ahead-
in-gene-editing-trials-1516562360)

~~~
vadimberman
Perfect, thanks!

So I guess it means about 2-3 years from now.

------
jfarlow
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](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...](http://science.sciencemag.org/content/sci/suppl/2018/02/14/science.aar6245.DC1/aar6245_Chen_SM.pdf)
(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/](https://serotiny.bio/pinecone/) (search
Cas13, REPAIR)

~~~
JumpCrisscross
What is Pinecone? Can I hack around with it as an individual?

~~~
jfarlow
Pinecone is our public protein design software. Feel free to play around.
Feedback is welcomed. We're trying to build an abstraction layer above DNA
sequences so you can build genetic tools to fulfill particular capabilities
without needing to know how to build DNA.

Or just to help teach what useful designs others have put out there - reveal
some of the 'magic' of current gene therapies or genetic editing tools. Some
interesting examples:
[https://serotiny.bio/notes/proteins/](https://serotiny.bio/notes/proteins/)

~~~
JumpCrisscross
Neat! What sorts of design decisions did you have to confront when designing
this language? Have you found it useful as a toy modelling space, _i.e._ where
suitably replicating real-world protein X in “code” reveals interesting things
about X?

~~~
jfarlow
A bit of a late reply, sorry, but it's a great question.

We found many design decisions we had to confront - more than we expected. The
largest two include 1) the decision to use an amino acid sequence as ground
truth (and _not_ DNA), and 2) the decision to make the language universally
proscriptive (at the cost of being universally descriptive).

Anything you build in the system can be altered, broken apart, and itself be
part of a larger whole - all while being manufacturable. But that comes at the
cost that there are certain highly complicated overlapping synergistic type
designs that just can't be made. Whereas with an entirely descriptive language
one can describe the multi-layered fugue that is the HIV genome - but the
construction rules become so lax that they lose their instructive
capabilities, and can no longer logically guarantee constructibility.

The most interesting (and surprising?) thing we learned is that we now have
the only data-structure that can reliable and efficiently answer questions of
the sort of, "show me any/all designs that utilize the protein, _GFP_".

------
stupandaus
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...

~~~
tomrod
With CRISPR such a promising technology, have the patent holders considered
relinquishing the patent?

~~~
ryanhuff
Not so far.

[https://www.nature.com/news/bitter-crispr-patent-war-
intensi...](https://www.nature.com/news/bitter-crispr-patent-war-
intensifies-1.22892)

------
indescions_2018
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](https://www.youtube.com/watch?v=gK3dcjBaJyo)

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

Using the existing systems of sensing/data-exfiltration already used by life.
Fireflies produce light, jellyfish glow, plants curl up in darkness, fungi
bud, flowers blossom, you blush, you sweat, you get hungry, etc.

Couple those outputs to a similar biological input: sensing DNA damage,
presence of particular DNA, small molecules, proteins, sugars, etc., sensing
of temperature, magnetic field, particular atom/ion, etc.

Couple them: if cold -> glow; if Iron -> blossom, if low blood sugar -> emit
light.

The recent "Chimeric Antigen Receptor" approved by the FDA is exactly one such
designed way to act on information within a cell; if cancer-like -> kill cell.

These CRISPR tools are similar; if presence of particular DNA -> change DNA,
or cut DNA, or activate response.

~~~
indescions_2018
There is an inherent poetic quality to the inner workings of nature and living
beings. Certainly synthetic biology should reflect that ;)

I also think you've hit upon something fundamental. The use of light and
photons as the lowest common denominator in biochemical function. Not just in
the optogenetic sense. But as the basic building block in biophysics.

~~~
jfarlow
And electrons. Amplify an energy difference/transfer to a shift in protein
conformation, to the cellular-scale presence/absence of noticable molecules,
to actions of cells that are collectively organized to respond, to tissues, to
organisms.

Optigenetic tools are just the most clear abstractions from photon->gene, but
the same principles apply to thermo-, mechano-, chemo-, etc-, protien sensors
(i.e. all of them).

They're all an amplification cascade from photons and electrons upwards. It is
elegant in how general that description is (and how it suggests an approach to
synthetic designs).

------
Ice_cream_suit
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...](http://science.sciencemag.org/content/early/2018/02/14/science.aaq0179)

------
Ice_cream_suit
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...](http://science.sciencemag.org/content/early/2018/02/14/science.aar6245)

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

------
ken
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.

------
qaq
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.

~~~
newnewpdro
I don't know how significant this [1] is a barrier to such treatments, but it
seems likely to be more of a potential problem for cures vs. sensors
w/potential false positives.

[http://newsroom.cumc.columbia.edu/blog/2017/05/30/crispr-
gen...](http://newsroom.cumc.columbia.edu/blog/2017/05/30/crispr-gene-editing-
can-cause-hundreds-of-unintended-mutations/)

------
make3
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

~~~
jfarlow
Companies using similar(-ish) technologies as applied to CRISPR directly:

Synthego: [https://tools.synthego.com/](https://tools.synthego.com/)

Desktop Genetics:
[https://www.deskgen.com/landing/](https://www.deskgen.com/landing/)

Open Source Community using deep learning for all sorts of biochemical and
genetic capabilities:

Deepchem: [https://deepchem.io/](https://deepchem.io/)

~~~
make3
thanks jfarlow. do you recommend any of them specifically?

~~~
jfarlow
Those are all run by great people and they do great work, pointed in
particulary interesting and different directions.

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

