
Gene Editing Could Make Anyone Immune to AIDS - nickb
http://blog.wired.com/wiredscience/2008/06/gene-editing-co.html
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ingenium
I didn't read the paper thoroughly yet, but from a brief skimming this is the
gist:

The technique they used was very clever. The first step was to take what's
called a zinc finger. This is a type of DNA binding protein that can
specifically recognize a sequence of DNA and bind to it. In this case, they
created two zinc fingers that bound to a region of the first transmembrane
domain (CCR5 has 7 transmembrane domains), just upstream of the deletion in
the delta32 mutation.

Then, attached to the zinc fingers is a type IIS restriction enzyme. What this
does is make a double stranded cut in the DNA. In other words, it cuts both
strands in half. The cell, sensing the damage, repairs it with nonhomologous
end joining (<http://en.wikipedia.org/wiki/Non-homologous_end_joining>). Due
to the nature of the cut, mutations are introduced in the repair process.

It seems in many cases, the mutations introduced are sufficient to disrupt the
CCR5 protein and make it non-functional. While it's not as much a "sure thing"
as the delta 32 mutation, which introduces a frameshift, it seems relatively
effective. They used an adenovirus to introduce their zinc fingers +
restriction enzyme, so this has the risks associated with using a virus as a
delivery system (ie cancer).

Link to paper: [http://www.scribd.com/doc/3746359/Establishment-of-
HIV1-resi...](http://www.scribd.com/doc/3746359/Establishment-of-
HIV1-resistance-in-CD4-T-cells-by-genome-editing-using-zincfinger-nucleases-)

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riahi
While this is an interesting technique, I wonder what effects the absence of
the cell marker has on normal immune function. As well, gene targeting for
therapy is exceptionally tricky; if you miss, you can seriously screw things
up.

~~~
eugenejen
5% to 14% of European population lacked of CCR-5, while almost none of Asians
and Africans lacks CCR-5. A theory about this phenomenon is the black
death/smallpox in middle ages in Europe attacked CCR5. And the survivors from
several black deaths/smallpox outbreaks were descendants of CCR5 mutation. So
theoretically we know how people can live with CCR5 mutation.

Of course, the immune system is complex. So maybe a healthy CCR-5 Delta 32
person needs some other mutations to keep functioning instead of just losing
CCR-5.

~~~
ingenium
The theory about the black death being the origin isn't correct. While it does
provide resistance to the plague, studies have shown that it originated well
before that time.

However, people without CCR5 receptors are slightly more susceptible to some
diseases, such as West Nile Virus.

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rms
Immune to all R5 strains of HIV-1, at least... someone with this mutation
could still get infected via direct blood transfusion from a late stage AIDS
patient.

