
New era of fast genetic engineering - prateekj
http://www.newscientist.com/article/mg22129530.900-right-on-target-new-era-of-fast-genetic-engineering.html#.Uuf4hXfTlok
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jere
>This is not a problem that can be solved by computers. Ultimately, there is
only one way to be sure what a particular bit of DNA does – you have to alter
it in real, living cells to see what happens.

Ah, the old "comment out this line" style of understanding code.

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rlwolfcastle
The debugger hasn't been born yet.

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WasimBhai
For those who are in this field, I have a question, and will be grateful for
an answer. How far-reaching is this technique can be for Cancer treatments? I
understand Cancer is not a simple disease that can be delineated.

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toufka
As a researcher in the field, it's a big question. There are lots of answers.
Most of the time, the answer will be, 'maybe, and maybe more if we can get it
to the right place at the right time - but it's often hard to know where/when
that is'.

More specifically, and more concretely, there are certain kinds of cancers
(and diseases/disorders) that this will be very effective against. And some
advanced iteration of this technology will be curative - entirely. This is of
an entirely different kind of medicine than bathing trillions of cells in a
potent chemical in the hopes that one of those molecules might slow another
molecule - somewhere. This kind of genetic engineering would enable a
biological feature to be entirely restored, changed, or removed.

Those cancers this will be effective against are those where a particular,
knowable, and targetable gene has a known and particular mutation. And this is
actually a large class of cancers. Cancers often initiate as mutations that
destroy the elaborate series of 'checkpoints' your body has instituted to
prevent runaway growth. If one of those proteins that guards against runaway
growth gets damaged, then there are far more ways to get cancer. If you can
repair that checkpoint (via (genetic) therapies), you can halt, slow, or even
destroy what caused that (particular) cancer. The analogy of the cells in your
body as a society is not a bad one. And cancer, as a 'criminal' is not
particularly dangerous to the whole. It only becomes dangerous when the
police, the courts, and the military are also crippled. And we have learned _a
lot_ about how those regulatory objects function in the past two decades.
However being able to restore them or affect them in a living being has been
orders of magnitude more difficult than simply watching to see what they do.
It would be fair to say we know understand most of the key elements, and many
of the details of their roles of what's happening in the society of your body.
However making direct changes to that society in a living being is still
tricky, and our tools blunt. What you see here is the sharpening of these new
tools - tools that offer the opportunity to restore (or improve) those
regulatory objects to a broken system.

To say it another way - there is no way I could imagine a cancer to be 'cured'
by small molecules (alone). Small molecules work great against 'the different'
\- but by definition, cancer is not different from its host. I think this is
why the drugs of the 20th century were so ineffective against cancer while
simultaneously so effective against parasites, bacteria and even viruses for
the most part. The only way I could (from first principles) expect to prevent
or alter a process like cancer is using tools like the ones talked about here.

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jstsch
How can knocking out a certain gene (for all cells in your body) kill a cancer
cell? For instance, for many cancer cells with a defect in 'P53' (a gene which
can induce cell death), knocking out this defective gene would not help -
would it?

Or would you need a two step process, like a molecule which connects to the
marker and then use a second step to knock-out a gene essential for cell
survival? Or can this technique be used to repair a certain gene?

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toufka
The most interesting part of the above tool is not its ability to _knock out_
a specific gene, but its ability to knock out a _specific_ gene. The key word
is 'specificity'. Knocking out is just the easiest proof of principle thing
you can do once you find a sequence. Finding it with specificity in a live
organism is the magnificent part.

There is an entire field dedicated to editing genetic code - and it's getting
really good. The issue is targeting it to the right spot in a live organism
(and conversely, not targeting your editing machinery to the wrong spot). If
you can get to it, there's lots you can do besides knocking out a gene. If we
call the p53 gene the judge or head executioner in our scheme above, it's
finding him that's the problem. If you can pinpoint the corrupt judge, you can
easily (relative to finding him) install a replacement. What you don't want to
do is accidentally replace your police force or your teachers with
judges/executioners (even if they're good ones) - and that ability to target
is the greatest issue with engineering the genetics of live cells currently.

(As a side note, this is EXACTLY what the HPV virus does - it runs around
assassinating that judge with relentless precision - and thus is a prime cause
for allowing cancer to run rampant. The vaccine against HPV prevents these
assassinations.)

Further, and only slightly more in the future, once you have access to the
genetics, you can start to run logic programs inside the cells. You can start
to release the (genetically encoded) tools IFF the cell is $cancerous, where
$cancerous is defined as a further set of genetic conditions within the cell.
In this way you could surveill the entire society while only targeting the bad
guys.

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jstsch
Right! I wasn't aware that the editing process is quite easy once you can
target a specific gene. Awesome! :)

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mbreese
Specifically, you can target just the _defective_ version of the gene. In
theory, your good copies could be ignored, only removing the bad genes from
the cancer tissue.

However, I don't think that this will ever be applied on a whole-body scale
because the off-target effects aren't well characterized at this point. That
is, of course, unless you have a bad cancer and have no other options. At that
point, having off-target effects is the least of your concerns.

The problem with gene editing in this context is that the changes are
permanent. So if you miss and edit a good cell, that cell is now damaged, or
may only have 1 good copy of a gene, and thus be more susceptible in the
future. In some cases, shRNA to silence a gene may prove more effective
because it is temporary.

Right now these are only used in the lab for research.

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matznerd
As a futurist, I love reading quotes like this:

"What used to take two years or more can now be done in six weeks, says Zhang.
"That's a big difference." For those who have spent years trying to make just
one or two specific changes to plants or animals, this is revolutionary.

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leobelle
What's a "futurist"?

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jere
The parent is obviously a "social scientist whose specialty is to attempt to
systematically explore predictions and possibilities about the future and how
they can emerge from the present, whether that of human society in particular
or of life on earth in general." Obviously.
[http://en.wikipedia.org/wiki/Futurist](http://en.wikipedia.org/wiki/Futurist)

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jostmey
I find it amusing that the underlying technology that made this study possible
was patented (end of page 1), but that a royalty free alternative solution was
found. In science people are often quick to patent each new breakthrough,
which sometimes just prevents other scientist from building on that initial
breakthrough. I think it is an important lesson to realize that not every new
discovery is worth patenting. Perhaps only when a technology is truly ready to
be brought to market in the foreseeable future should a patent be considered.
Otherwise, the patent could become a distraction to the importance of the
breakthrough itself.

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skosuri
All the technologies described in this article have many competing patent
claims by academics at Harvard, MIT, Berkeley, and a few others. Obviously
it's hard to tell right now which patents will go through, but I'm pretty sure
they won't be royalty free. The main difference is that the procedure is now
so easy that most academics will just infringe.

