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Three challenges with CRISPR: - find right change to make - make that change in target cell without any off-target changes to other genes. - efficiency - bei

Three challenges with CRISPR: - find right change to make - make that change in target cell without any off-target changes to other genes. - efficiency - being able to change enough of the cells to have the desired effect. The last one is probably the hardest if the cell type isn't something you can easily take out of the body, change, grow up and put back.

EamonnMR 7y ago
In this case it would be "remove, treat, and re-implant all of the bone marrow" I think. Better than trying to CRISPR your brain or heart I'd imagine, but much harder than, say, skin.
The_rationalist 7y ago
What are the "high score" for efficiency? Did researchers tried and were successful at modifying a whole organ, a whole body?
- DrScientist 7y ago
  The human body contains 35-40 trillion cells. By far the best way to make a whole body change would be to change one cell ( the embyro/egg/sperm ) and let nature take it's course - however that has the 'playing god with human evolution' concern. Delivery mechanisms are key - you have to get your therapeutic inside each cell - this is hard and even harder to do in a cell type specific way. It's much easier to do ex-vivo than in-vivo: ( see the diagram on this page ) http://www.crisprtx.com/gene-editing/therapeutic-approach http://www.crisprtx.com/gene-editing/therapeutic-approach How many cells you need all depends on the biology of what you are trying to do - there is no universal answer. So you might need a small number cells if you are changing the messages the changed cells send to other cells through control networks. In other cases, where the change only changes that cell - you might need to change a large number to see an effect.
  - airstrike 7y ago
    > 'playing god with human evolution' concern Don't mean to derail this entire thread, but even as someone who believes in God, I find it increasingly harder to understand what objectively is wrong about these purported ethical dilemmas (e.g. cloning)
    - judah 7y ago
      > I find it increasingly harder to understand what objectively is wrong about these purported ethical dilemmas (e.g. cloning) Believer in God here, and, like you, I find these "playing God" concerns to be largely unfounded, and often based in fear-of-the-unknown more than objectivity. In the 18th and 19th centuries, some religious groups opposed surgery because it was playing god; "disfiguring the divine image." But today, we religious people almost invariably welcome such medical advances: the good they do far outweighs any theoretical fear-based concerns. I think the same will happen with modern medical advances. And, theologically in the Jewish and Christian Bible, God has given humans dominion over nature. I see medical advances -- including surgery, blood transfusions, vaccines, and yes, gene editing -- as exercising that dominion to help heal people and reduce suffering.
      - DrScientist 7y ago
        Gene editing on an embryo involves making a choice for an unborn person without possibility of consent - and their children, and their children etc. That assumption of knowing better than the person affected is 'playing god' in a way that doing a surgical procedure on a consenting person isn't. Obviously that stuff is already done today - abortion or medical intervention at an early stage where the parent acts on behalf of the person. One of the things that's different is the scope and power of these techniques. Look at the diversity of domestic dogs, from great danes to toy dog breeds - that all came through selective breeding from the same wolf ancestor in a few thousand years. Also remember that humans are 99% the same as chimps at the DNA level and about 85% with mice. Direct, untrammeled genetic modification of humans could unleash huge changes in a very short time. Until we are clear about how we want to manage that, it's easier to have a moratorium.
peter303 7y ago
I read somewhere efficiency is 10%-20%. That may be fine to fix a condition where you need to add a new protein, e.g. muscular dystrophy. However, maybe not so well where you need to subtract. If you can pose an HIV therapy as the former- say make 10% of the T-cell stem cells infection-proof, then that could work. On the other hand, hoping the remove all the retro-inserted HIV DNA probably wont work.

EamonnMR 7y ago

In this case it would be "remove, treat, and re-implant all of the bone marrow" I think. Better than trying to CRISPR your brain or heart I'd imagine, but much harder than, say, skin.

The_rationalist 7y ago

What are the "high score" for efficiency? Did researchers tried and were successful at modifying a whole organ, a whole body?

DrScientist 7y ago
The human body contains 35-40 trillion cells. By far the best way to make a whole body change would be to change one cell ( the embyro/egg/sperm ) and let nature take it's course - however that has the 'playing god with human evolution' concern. Delivery mechanisms are key - you have to get your therapeutic inside each cell - this is hard and even harder to do in a cell type specific way. It's much easier to do ex-vivo than in-vivo: ( see the diagram on this page ) http://www.crisprtx.com/gene-editing/therapeutic-approach http://www.crisprtx.com/gene-editing/therapeutic-approach How many cells you need all depends on the biology of what you are trying to do - there is no universal answer. So you might need a small number cells if you are changing the messages the changed cells send to other cells through control networks. In other cases, where the change only changes that cell - you might need to change a large number to see an effect.
- airstrike 7y ago
  > 'playing god with human evolution' concern Don't mean to derail this entire thread, but even as someone who believes in God, I find it increasingly harder to understand what objectively is wrong about these purported ethical dilemmas (e.g. cloning)
  - judah 7y ago
    > I find it increasingly harder to understand what objectively is wrong about these purported ethical dilemmas (e.g. cloning) Believer in God here, and, like you, I find these "playing God" concerns to be largely unfounded, and often based in fear-of-the-unknown more than objectivity. In the 18th and 19th centuries, some religious groups opposed surgery because it was playing god; "disfiguring the divine image." But today, we religious people almost invariably welcome such medical advances: the good they do far outweighs any theoretical fear-based concerns. I think the same will happen with modern medical advances. And, theologically in the Jewish and Christian Bible, God has given humans dominion over nature. I see medical advances -- including surgery, blood transfusions, vaccines, and yes, gene editing -- as exercising that dominion to help heal people and reduce suffering.
    - DrScientist 7y ago
      Gene editing on an embryo involves making a choice for an unborn person without possibility of consent - and their children, and their children etc. That assumption of knowing better than the person affected is 'playing god' in a way that doing a surgical procedure on a consenting person isn't. Obviously that stuff is already done today - abortion or medical intervention at an early stage where the parent acts on behalf of the person. One of the things that's different is the scope and power of these techniques. Look at the diversity of domestic dogs, from great danes to toy dog breeds - that all came through selective breeding from the same wolf ancestor in a few thousand years. Also remember that humans are 99% the same as chimps at the DNA level and about 85% with mice. Direct, untrammeled genetic modification of humans could unleash huge changes in a very short time. Until we are clear about how we want to manage that, it's easier to have a moratorium.

peter303 7y ago

I read somewhere efficiency is 10%-20%. That may be fine to fix a condition where you need to add a new protein, e.g. muscular dystrophy. However, maybe not so well where you need to subtract. If you can pose an HIV therapy as the former- say make 10% of the T-cell stem cells infection-proof, then that could work. On the other hand, hoping the remove all the retro-inserted HIV DNA probably wont work.