

MIT develops new method to cure broad range of viruses - tq41
http://bostinnovation.com/2011/08/04/mit-researchers-develop-new-method-to-cure-a-broad-range-of-viruses/

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alexholehouse
These DRACO proteins are (in the grand scheme of things) non-sequence (or
indeed virus) specific, which is one of the reasons this is so exciting. They
are specific in terms of the dsRNA binding domain they’re built with, although
these domain may have a range of different sequences or secondary structures
they can bind. The apoptotic response is triggered by the DRACO proteins
crosslinking when two of them bind to the same fragment of dsRNA.

Put into slightly more straight forward terms, the apoptotic pathway is like a
massive self destruct switch, which is triggered by a whole range of different
things (viral infection, DNA damage, cancer signals etc). The body has evolved
various mechanisms to detect dsRNA, as this is often a sign of viral
infection. dsRNA doesn't occur naturally in mammals beyond ~10-25 nucleotides
in length, while many viruses either have a dsRNA genome, or create long
strands of dsRNA during their replication cycle, even if they do not have a
long-term stable dsRNA genome. I’d imagine this provides a mechanism for DRACO
proteins to target these non-dsRNA viruses. These DRACO proteins are simply a
way to supercharge the body’s defences, increasing the cell's sensitivity to
dsRNA.

My main concern would be relating to an immune response (any kind of
recombinant protinaceous therapeutics is often risky), and also regarding
administration and pharmacokinetics. Viruses are good at making lots of
themselves, and may accumulate in different cell types, tissues or organs.
Getting good, thorough coverage of the body may be a challenge. However, that
said, any kind of “outside the box” therapeutics is always very welcome,
especially where apoptosis is concerned, as it’s implicated in a wide range of
diseases but is still relatively poorly understood.

~~~
intended
I'm curious - I remember that over time viruses been incorporated into our DNA
and rendered inert. Could these be targeted and damaged by the DRACO system?
Or would they come within the ~10-25 nucleotide limit?

~~~
alexholehouse
So the viruses incorporated into our DNA are in fact fragments of viral DNA,
typically from reverse transcriptases. The DRACO proteins recognizes double
stranded RNA (dsRNA), while reverse transcriptases incorporate dsDNA into our
genome, and then use our own DNA replication proteins to make more of
themselves! Crafty! The upshot of this, though, is that there's no dsRNA in
our genome, so nothing the DRACO could detect.

It's like we store our genome on DVD, and some viruses use CDs. They're very
similar, but it's not the "content" the DRACO proteins are looking at, but the
medium. We have no way to make CDs, only viral proteins can do that, so if the
DRACO proteins see CDs, there's probably a virus about.

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pak
I am not convinced, especially when the company is hyping it to kill
"virtually all" viruses. Far from the majority of viruses contain dsRNA. For
example, the Ebola virus and rhinoviruses, which cause the common cold, all
contain an ssRNA genome. (For this reason I am confused why somebody quoted in
the article specifically uses these examples.) HPV and many other categories
of virus [1] contain only DNA. It would seem that only this category [2] of
viruses would be affected.

[1] <http://en.wikipedia.org/wiki/DsDNA_virus>

[2] <http://en.wikipedia.org/wiki/Double-stranded_RNA_viruses>

~~~
carbocation
You're talking about the contents of the virus capsid.

DRACO works by killing cells that contain viral dsRNA, which will include
cells infected by most kinds of DNA and RNA viruses, because those viruses
usually have a dsRNA stage.

~~~
pak
I don't believe that any DNA virus would replicate via a dsRNA intermediate,
since that would be an unnecessary step and therefore anti-selective. You are
correct that ssRNA viruses create a dsRNA template while replicating but I
would think that this state is transient and therefore not a great target,
unless this treatment can target dsRNA strands littered with replication
forks.

~~~
carbocation
Sorry, 'stage' was misleading. As described in the PLOS ONE article on this
subject, they typically undergo symmetrical transcription. So more accurately,
dsRNA & ssRNA viruses typically go through a dsRNA stage. DNA viruses
typically produce dsRNA during transcription.

------
JunkDNA
You have to read to the end to find out that it has only been confirmed in
mice. We have cured practically every major medical condition in mice. The
human part is the hard part. I'm skeptical that this mechanism wouldn't have
some pretty severe side effects.

~~~
praptak
_"It’s bad enough that I live in a country that ranks 37th in health care. The
thing that really pisses me off is that I have worse health care than mice."_
\- Scott Adams, "Frequently Disappointed by Mice"

[http://dilbertblog.typepad.com/the_dilbert_blog/2007/06/freq...](http://dilbertblog.typepad.com/the_dilbert_blog/2007/06/frequently_disa_1.html)

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jleader
I'm curious why bostinnovation.com posts get voted up so high on HN, when
they're so full of hype, and so lacking in content. This one is at least
intrinsically more interesting than the last one I saw, "a list of programming
language designers who have driven past Boston".

~~~
kmccarth
jleader, I am the author of this post and the 'programming languages who have
driven past Boston' article. I literally laughed out loud when I read your
comment. I was surprised when that post was on Hacker News myself (I knew it
wasn't my best). I promise to do better :)

~~~
jleader
Glad to hear it!

As a resident of Los Angeles, and graduate of Caltech, I'm completely
sympathetic to trying to get the word out about tech innovations happening in
places other than Silicon Valley.

------
bugsbunnyak
Press release: <http://www.ll.mit.edu/news/DRACO.html>

Journal article (open access, hooray!)
[http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjourna...](http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0022572)

------
shabble
This is coming from a non-biological background, and hence may contain
ridiculous ideas:

Would it be possible to devise some sort of virus which could somehow
'checksum' a given cell's DNA, and trigger cell-death if it doesn't match?

I've no idea if that is even possible, or whether it'd require a custom virus
per-person (or whether you could add some sort of 'training stage' by
introducing it to clean host DNA first)

Another tricky problem would be making sure it hits every/enough cells to kill
the other virus, but slowly enough that there's time for the body to replace
them. And of course, that the virus checksums itself regularly and self-
terminates on mutation.

~~~
athom
Actually, you wouldn't want to do that. A lot of human cells actually
rearrange their genome as part of their normal function. This is how
lymphocytes come up with antibodies, for example.

By selecting and rearranging several different coding sequences from three
different chromosomes, each lymphocyte develops its own antibody "design",
permanently changing its own genome in the process. This is what allows us to
develop immunity to a broad range of foreign antigens with a relatively small
amount of genetic code. Think of it as an "immune alphabet", if you will. You
certainly _don't_ want to interfere with that!

Other rearrangements also occur, some harmful, others not so much. Even if you
wanted to target just the bad ones, though, a virus really isn't the tool for
it. Your cytoxic T lymphocytes already do that. In fact, what you're really
describing isn't all that far off from what we already have. I think we even
have mechanisms for genetic error correction and repair, but I'll have to hit
the books again to double-check that.

~~~
shabble
Thanks for the detailed answer, you've given me a bunch of stuff to go read
about. My original idea came from something from SENS about moving
mitochondrial DNA into the nucleus to take advantage of the better repair
systems: <http://www.sens.org/sens-research/research-themes/mitosens>

Obviously it would be more complex than

    
    
        if hash(nuclear DNA) != clean_DNA_hash) die;
    

but I wonder to what extent the immune system could be enhanced. I wonder if
there are some techniques that could be adapted from the computer
virus/malware detection field back into biology.

A recent article on creating false-positives for a virus scanner
(<http://lock.cmpxchg8b.com/aids8064.html>) by analysing the signatures makes
me think of creating 'virus pre-images' for vaccination.

Other than the specialised cells which manipulate their own genome, would
there be value in positively checksumming {D,R}NA, rather than adaptively
pattern-matching for the bad ones, which is (I think) how it mostly works now?

Granted, you'd be hindering the evolutionary process by preventing mutation,
but if we ever intend to start messing around inside ourselves, the first step
would probably be to make sure that whatever we create, it's going to stay
that way, or die.

~~~
intended
One interesting thing to remember about the human immune system is that its
always on - IE it spends more time correctly identifying something as NOT
THREAT, than it does spending time finding THREAT. Mucking about with this
could have extreme consequences, a la auto-immune diseases for example.

------
Someone
Can someone fix that title? The viruses aren't cured, they are killed.

Also, are we sure that killing "a broad range of viruses" in one's body is a
good idea? Killing "a broad range of bacteria" certainly is not.

------
po
What about a virus like Herpes which enters a nerve cell? My understanding is
that nerve cells have extremely long lifespans so inducing apoptosis in them
has the potential to destroy physical sensation no?

~~~
JoeAltmaier
VIruses will kill the cell anyway. This kills it before the virus has a chance
to reproduce. Or do I have that wrong?

~~~
po
I think you have that wrong. The virus travels up the nerve into the cell
body. It stays there until the nerve (or you) dies. There it hijacks the
cell's DNA machinery to create more virus. These new viruses travel back down
the axion to be released in the blister. A cold sore on your lip is just the
herpes virus shedding new viruses. Once infected, the body develops antibody
to that type of the virus so infection doesn't spread but by then it's too
late. Usually the site also becomes asymptomatic over time as well, however
the virus will chill out in that nerve reproducing itself forever.

------
VladRussian
>DRACO selectively induces apoptosis, or cell suicide, in cells containing any
viral dsRNA [, which is RNA with two complementary strands that id the genetic
material of some viruses], rapidly killing infected cells without harming
uninfected cells.

and for the cases when pretty much all the cells of specific type are already
infected?

~~~
smallblacksun
Most viruses kill the host cell, or at least render it incapable of performing
its normal function, so if most of the cells of a type are infected you are in
trouble anyway.

~~~
intended
Well, despite the qualifier MOST viruses, I would have to point out that some
viruses end up being in your system without destroying their host cell - for
example HSV.

Ideally a way to excise the viral code from the cell would be found. DRACO
basically activates the destructor on a cell and ends the entire cell, even if
it is still serving the body.

I also recall that our chromsomes contain the genomes of viruses that have
been overcome over the span of our species life on this planet. Whether these
fragments would get affected is something I'm curious about.

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Apocryphon
If this was to backfire, it sounds like something out of dystopian sci-fi.

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ww520
For a moment I thought it's the curing of a broad range of computer viruses,
which can more likely be done than biological viruses. Reading the article
cured my misconception. The technique is still impressive.

------
sagarun
can't this "cure" fix HIV ?

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logjam
I would have a number of questions about this study, which was apparently run
and written up by the "DRACO" patent holder.

The results are largely from cell culture so any talk about a "cure for a
broad range of viruses" in the press release is premature bullshit to say the
least.

There were some _mice_ studies, along with this statement in the paper: "We
have also demonstrated that DRACOs can rescue mice challenged with H1N1
influenza" - for which evidence are examination of harvested organs after two
days, and three graphs showing separation for mortality between treatment and
control (buffer) groups out 10 days or so (time plot ends at that point).
Searching the paper, I finally find by looking at the morbidity graph that
we're talking about 13 mice per group for one type of DRACO intraperitoneal
administration, 5 per group for the other type of DRACO i.p, and 12 mice per
group for intranasal administration.

In addition, as the authors themselves note, how much cell death could be
tolerated in the face of _chronic_ viral infection remains to be seen.

This is a very preliminary trial. There are _years_ of work before this even
approaches meriting mention of a "cure".

------
Qa8BBatwHxK8Pu
how much portion of cells can human lose before getting into trouble? ...per
organ or other cell groups?

------
ChuckMcM
Unfortunately viruses may also be an agent for evolution [1]. This discovery
is basically a means to kill cells that match a particular rDNA sequence.
Seems like something that could become a very strange tool or a very horrible
weapon.

[1]
[http://www.newyorker.com/reporting/2007/12/03/071203fa_fact_...](http://www.newyorker.com/reporting/2007/12/03/071203fa_fact_specter)

~~~
athom
This is what your normal immune defenses already do. While some white blood
cells (neutrophils, monocytes) fight bacteria by "eating" them, viruses are
too small to be directly attacked this way. Instead, they cells they infect
have to be destroyed before they can release their viral burden. That's what
cytotoxic T cells do. They recognize antigens on infected cells, and kill them
by triggering apoptosis (programmed cell death).

What is _truly_ unfortunate is, this doesn't always work. Some viruses are
able to "hide" in their host cells, preventing them from activating the immune
response, and persist idefinitely in a latent state. This is why you can't
really get rid of herpes, once you have it.

What looks promising about this development is that it seems to target a
_form_ of RNA that is simply _not found_ in healthy cells. Human cells store
their genome in double-stranded DNA, and use _single_ -stranded RNA for
transcription, but make no use of _double_ -stranded RNA. Apparently, only
certain viruses do, so the presence of dsRNA in a human cell should be
diagnostic for viral infection, regardless of its sequence. In other words:
see dsRNA, kill it!

Would that all viruses were that easy.

