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There are first of all the obvious worries about the impact of genetic engineering. But worse than that is the method described on Radiolab where the genetic ch

There are first of all the obvious worries about the impact of genetic engineering. But worse than that is the method described on Radiolab where the genetic changes produce more instances of CRISPR itself so it passes along from generation to generation. But worse than that is the idea of CRISPR being airborne such that it can infect and change all of our genetics. Or the genetics of only some particular targeted subset of the population.

Para2016 10y ago
That sort of sounds like a familial prion disease but really - I don't see that as a legit concern. The enzyme is already present in Strep pyogenes which is practically ubiquitous. A lot of us have that same bacteria colonized in our throats. I never used CRISPR when I worked in a molecular lab, just a TOL2 system which was pretty cool in its own right. But CRISPR needs a DNA probe (probes are attached to CRISPR to target very specific sequences of DNA for editing) and a way to deliver itself into the cell. I didn't read the paper myself, but I'm guessing they just do a little microinjection of CRISPR into the embryo. And these gene edits for various hemoglobinopathies (G6PD and thalassemia), while impressive, are very simple. These are very specific mutations that when fixed, should yield a normal/working protein and a healthy phenotype.
- caustiko 10y ago
  Thanks for replying. I'm a layman in this field, so I'm not quite sure about how to parse your response. But wanted to make sure you were aware of the existence of Gene Drive. To me it seems dangerous, but I'd love to hear thoughts from someone more educated in the topic: https://en.wikipedia.org/wiki/CRISPR#Gene_drive https://en.wikipedia.org/wiki/CRISPR#Gene_drive This is the point where my thought process forked off into wondering about the implications if the capabilities of Gene Drive could somehow become airborne.
  - Para2016 10y ago
    Gene Drive with CRISPR is pretty neat, thanks for sharing, I honestly haven't worked with molecular techniques in over 4 years now, so it's been quite a while since I've reviewed a lot of this kind of stuff. From the gene drive wiki, this is one of my favorite lines: "Endonuclease gene drives work by cutting chromosomes that do not encode the drive at a specific site, inducing the cell to repair the damage by copying the drive sequence onto the damaged chromosome. This is derived from genome editing techniques and similarly relies on the fact that double strand breaks are most frequently repaired by homologous recombination if a template is present, and less often by non-homologous end joining. The cell then has two copies of the drive sequence." So that is pretty sweet. The researcher just hijacked the cell's repair mechanism in order to ensure the gene is present in both chromosome copies (I'm assuming the human 2n chromosomes here). That mean's all sexual progeny (zygote) will have to inherit one of these copies - and once that happens the single copy can duplicate itself by breaking the chromosome received from the other mating partner and then replicating the gene/drive via homologous repair. If you want to say it could be dangerous then yea, I'll agree with you. It would obviously depend on the gene you would include with the gene drive (the gene drive I'm assuming is just the homing endonuclease and RNA guide sequence used to target the drive-less chromosome). If a deleterious gene somehow managed to attach itself to the drive system - either artificially or randomly acquiring the sequence in vivo, then that person may have permanently ruined their chances for normal offspring. As far as an "airborne" vector with the gene drive/and bad gene someone wanted to be propagated, that would be a lot harder I think. I believe you would need the vector to be a virus, so it could gain access to the host's cells and DNA. So you would need a pretty high powered lab working extensively to make an infectious but not virulent virus - with the gene drive and harmful gene it carries. Those labs would be highly regulated and controlled bio weapons facilities. So yea, it could be dangerous. Or it could be fantastic and something like this could be used to cure all of sickle cell disease by coding for a normal beta hemoglobin gene. Sickle cell only occurs from a single amino acid change, it's not a super complicated genetic disease. It's just one amino acid change that causes red blood cell sickling shape and fragility - which leads to a lot of pain and eventual early demise. There are other genetic diseases that are very simple that could be cured as well. Anyways, sorry for the late response. I think there is potential to do a lot of good and a lot of harm with this technology. Let's hope we keep it in the right hands.

Para2016 10y ago

That sort of sounds like a familial prion disease but really - I don't see that as a legit concern. The enzyme is already present in Strep pyogenes which is practically ubiquitous. A lot of us have that same bacteria colonized in our throats. I never used CRISPR when I worked in a molecular lab, just a TOL2 system which was pretty cool in its own right. But CRISPR needs a DNA probe (probes are attached to CRISPR to target very specific sequences of DNA for editing) and a way to deliver itself into the cell. I didn't read the paper myself, but I'm guessing they just do a little microinjection of CRISPR into the embryo. And these gene edits for various hemoglobinopathies (G6PD and thalassemia), while impressive, are very simple. These are very specific mutations that when fixed, should yield a normal/working protein and a healthy phenotype.

caustiko 10y ago
Thanks for replying. I'm a layman in this field, so I'm not quite sure about how to parse your response. But wanted to make sure you were aware of the existence of Gene Drive. To me it seems dangerous, but I'd love to hear thoughts from someone more educated in the topic: https://en.wikipedia.org/wiki/CRISPR#Gene_drive https://en.wikipedia.org/wiki/CRISPR#Gene_drive This is the point where my thought process forked off into wondering about the implications if the capabilities of Gene Drive could somehow become airborne.
- Para2016 10y ago
  Gene Drive with CRISPR is pretty neat, thanks for sharing, I honestly haven't worked with molecular techniques in over 4 years now, so it's been quite a while since I've reviewed a lot of this kind of stuff. From the gene drive wiki, this is one of my favorite lines: "Endonuclease gene drives work by cutting chromosomes that do not encode the drive at a specific site, inducing the cell to repair the damage by copying the drive sequence onto the damaged chromosome. This is derived from genome editing techniques and similarly relies on the fact that double strand breaks are most frequently repaired by homologous recombination if a template is present, and less often by non-homologous end joining. The cell then has two copies of the drive sequence." So that is pretty sweet. The researcher just hijacked the cell's repair mechanism in order to ensure the gene is present in both chromosome copies (I'm assuming the human 2n chromosomes here). That mean's all sexual progeny (zygote) will have to inherit one of these copies - and once that happens the single copy can duplicate itself by breaking the chromosome received from the other mating partner and then replicating the gene/drive via homologous repair. If you want to say it could be dangerous then yea, I'll agree with you. It would obviously depend on the gene you would include with the gene drive (the gene drive I'm assuming is just the homing endonuclease and RNA guide sequence used to target the drive-less chromosome). If a deleterious gene somehow managed to attach itself to the drive system - either artificially or randomly acquiring the sequence in vivo, then that person may have permanently ruined their chances for normal offspring. As far as an "airborne" vector with the gene drive/and bad gene someone wanted to be propagated, that would be a lot harder I think. I believe you would need the vector to be a virus, so it could gain access to the host's cells and DNA. So you would need a pretty high powered lab working extensively to make an infectious but not virulent virus - with the gene drive and harmful gene it carries. Those labs would be highly regulated and controlled bio weapons facilities. So yea, it could be dangerous. Or it could be fantastic and something like this could be used to cure all of sickle cell disease by coding for a normal beta hemoglobin gene. Sickle cell only occurs from a single amino acid change, it's not a super complicated genetic disease. It's just one amino acid change that causes red blood cell sickling shape and fragility - which leads to a lot of pain and eventual early demise. There are other genetic diseases that are very simple that could be cured as well. Anyways, sorry for the late response. I think there is potential to do a lot of good and a lot of harm with this technology. Let's hope we keep it in the right hands.