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This is a good summary, and I can follow up on a couple points. (I don’t have direct experience with Crispr data, but I’m currently a PhD student in a computati

This is a good summary, and I can follow up on a couple points. (I don’t have direct experience with Crispr data, but I’m currently a PhD student in a computational genomics program, and have 4 years of experience in a lab that does crispr experiments in addition to my projects.) Related to both the idea of inserting DNA and off target effects - the issue is that scientists can engineer a cut, but then rely on the cell’s repair mechanisms to “stitch” the cut DNA back together. These mechanisms are inherently stochastic and error prone and are how many somatic mutations, such as those in cancer cells, arise. So for off target effects, even if you make the cut at the right place, you can still end up with new unintended SNPs and indels nearby. And for inserting new DNA, it’s not a guarantee. You can provide the template that you want to incorporate, but it might get missed, or get copied in more than once or in the wrong orientation.

subroutine 7y ago
IMO the biggest concern is not whether CRISPR-Cas9, and DNA ligase, will do their job reliably (given appropriate guide RNA, and methodology)... the biggest concern to me is that we don't know what else the target SNP tends to do, aside from whatever we've found from GWAS. Here's an example... APOE e4 is associated with Alzheimer's disease risk. People in Guatemala have a high prevalence of this allele. Some researchers from the US might decide it's a good idea to fly down to Guatemala and launch a CRISPR clinical trial to 'protect' newborn Guatemalans from this increased risk of Alzheimer's. So they do; come back to the US, have a toast to longevity for these children. It has recently come to light however, that APOE e4 confers protection against Malaria parasites. Not a big deal if you live in Norway - huge deal if you live in Guatemala. Suddenly, the risk of developing an age related dementia doesn't seem all that pertinent. So, my 2 cents is that, if we're really going to start CRISPRing babies, we'd better be doing our due diligence, and for now limit to diseases that significantly and immediately impair wellbeing.

subroutine 7y ago

IMO the biggest concern is not whether CRISPR-Cas9, and DNA ligase, will do their job reliably (given appropriate guide RNA, and methodology)... the biggest concern to me is that we don't know what else the target SNP tends to do, aside from whatever we've found from GWAS. Here's an example... APOE e4 is associated with Alzheimer's disease risk. People in Guatemala have a high prevalence of this allele. Some researchers from the US might decide it's a good idea to fly down to Guatemala and launch a CRISPR clinical trial to 'protect' newborn Guatemalans from this increased risk of Alzheimer's. So they do; come back to the US, have a toast to longevity for these children. It has recently come to light however, that APOE e4 confers protection against Malaria parasites. Not a big deal if you live in Norway - huge deal if you live in Guatemala. Suddenly, the risk of developing an age related dementia doesn't seem all that pertinent. So, my 2 cents is that, if we're really going to start CRISPRing babies, we'd better be doing our due diligence, and for now limit to diseases that significantly and immediately impair wellbeing.