4 ms·

Thanks for the explanation. >the off target effects are much more difficult to prevent Why is that the case? And are there any promising theories for how we m

Thanks for the explanation. >the off target effects are much more difficult to prevent Why is that the case? And are there any promising theories for how we might overcome that problem? CRISPR has already been approved for some forms of gene therapy. I assume that's because, for people with crippling diseases, the benefits clearly outweigh the risk. But going forward, as we address less crippling diseases, how do you grok the known benefit/unknown costs of using CRISPR for a cure? This will be an even bigger problem once CRISPR is used for more superficial or cosmetic things. We need to create a decision model and quantify the risks as much as possible. I have a feeling that countries will "compete" on taking risks with CRISPR. For example, China might see CRISPR as a way to increase its dominance on the world stage. If there's a risky way for CRISPR to increase intelligence, they might take the risk, because China has more to gain than America.

ImaCake 6y ago
>Why is that the case? And are there any promising theories for how we might overcome that problem? I am still quite new to CRISPR so I am unsure what people are doing to solve this problem. As for why, I would say that the problem is that, like most proteins, Cas9 just bounces around using brownian motion and there is always just some probability of it being near the wrong piece of DNA at the right time. There's not much that can be done about that! However, we can do something about Cas9's binding affinity to sequences that are similar, but not idetnical, to the target sequence. One could imagine Cas9 binding (with lower affinity) to a sequence of 20 bases that is incorrect on a couple of bases. Indeed, much of the off-target effects come from this. So if one could modify Cas9 to only bind to the exact sequence that should reduce off-target mutations.

ImaCake 6y ago

>Why is that the case? And are there any promising theories for how we might overcome that problem? I am still quite new to CRISPR so I am unsure what people are doing to solve this problem. As for why, I would say that the problem is that, like most proteins, Cas9 just bounces around using brownian motion and there is always just some probability of it being near the wrong piece of DNA at the right time. There's not much that can be done about that! However, we can do something about Cas9's binding affinity to sequences that are similar, but not idetnical, to the target sequence. One could imagine Cas9 binding (with lower affinity) to a sequence of 20 bases that is incorrect on a couple of bases. Indeed, much of the off-target effects come from this. So if one could modify Cas9 to only bind to the exact sequence that should reduce off-target mutations.