3 ms·

Gene Editing Could Make Anyone Immune to AIDS

8 points by nickb 18y ago

riahi 18y ago
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.
- jamongkad 18y ago
  I think that's what set the premise for the movie "I am Legend".
- eugenejen 18y ago
  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 18y ago
    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.
rms 18y ago
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.
ingenium 18y ago
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 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-resistance-in-CD4-T-cells-by-genome-editing-using-zincfinger-nucleases- http://www.scribd.com/doc/3746359/Establishment-of-HIV1-resi...

8 points by nickb 18y ago

riahi 18y ago

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.

jamongkad 18y ago
I think that's what set the premise for the movie "I am Legend".
eugenejen 18y ago
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 18y ago
  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.

rms 18y ago

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.

ingenium 18y ago

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 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-resistance-in-CD4-T-cells-by-genome-editing-using-zincfinger-nucleases- http://www.scribd.com/doc/3746359/Establishment-of-HIV1-resi...