Agree in principle. But I would argue that we should include germline gene editing. People at risk for having a child with a genetic disease would benefit. Delivery is easier and is far more cost-effective than somatic gene therapy. And yes, even though embryo selection is currently an option, germline gene editing would still be beneficial, especially in cases where the female partner is older and there are fewer embryos generated per IVF cycle.
The SAGE framework makes alot of sense when you think about the pipeline inversion, going from product-centric to patient-centric queues. I worked adjacent to a clinical trial team once and the economics just never penciled for ultra-rare conditions. Treating each customized edit as a procedure rather than a novel therapeutic bypasses the blockbuster model entirely, which honestly feels overdue for cases like Baby KJ's.
It’s tricky because CRISPR based editing is not as simple as it’s portrayed here. Each time you design a guide RNA there is potential for off target effects. So essentially custom targets for each individual are a “different medicine”. We don’t know for sure how each will behave in individual patients. Patients will need to know the risk…there is a strong chance it could correct the genetic defect and a some level of probability there could be off target side effect. One other complication is not all targets are the same in the genome…some genes share great similarities in coding or exonic sequence. The specificity of loci to be corrected would likely require screening of the reagents required to meet a certain efficacy before it could be applied to the human body. Delivery is also no walk in the park…how do you correct a gene with a germline mutation that is primiarily expressed in liver as opposed to circulating lymphocytes etc. While the SAGE idea is interesting we are so far away from this technology being ready to go for any possible case. There is also the other complication of diseases modified by epigenetic effects or even gene-gene interactions. So in other words there may only be a limited number of rare diseases editing will be available. Just like precision medicine, we can identify somatic mutations in tumors that give indication to the drug the patient is most likely to respond to, or likely to kill most of the tumor. However, just like germline editing, precision oncology is mostly limited by the drugs available and there is still limited knowledge why say genetic features predict some effects for some but not for others. I like the idea of SAGE but putting this into practice is going to be challenging and editing will not be as so widely available as this article portrays it.
Agree in principle. But I would argue that we should include germline gene editing. People at risk for having a child with a genetic disease would benefit. Delivery is easier and is far more cost-effective than somatic gene therapy. And yes, even though embryo selection is currently an option, germline gene editing would still be beneficial, especially in cases where the female partner is older and there are fewer embryos generated per IVF cycle.
The SAGE framework makes alot of sense when you think about the pipeline inversion, going from product-centric to patient-centric queues. I worked adjacent to a clinical trial team once and the economics just never penciled for ultra-rare conditions. Treating each customized edit as a procedure rather than a novel therapeutic bypasses the blockbuster model entirely, which honestly feels overdue for cases like Baby KJ's.
It’s tricky because CRISPR based editing is not as simple as it’s portrayed here. Each time you design a guide RNA there is potential for off target effects. So essentially custom targets for each individual are a “different medicine”. We don’t know for sure how each will behave in individual patients. Patients will need to know the risk…there is a strong chance it could correct the genetic defect and a some level of probability there could be off target side effect. One other complication is not all targets are the same in the genome…some genes share great similarities in coding or exonic sequence. The specificity of loci to be corrected would likely require screening of the reagents required to meet a certain efficacy before it could be applied to the human body. Delivery is also no walk in the park…how do you correct a gene with a germline mutation that is primiarily expressed in liver as opposed to circulating lymphocytes etc. While the SAGE idea is interesting we are so far away from this technology being ready to go for any possible case. There is also the other complication of diseases modified by epigenetic effects or even gene-gene interactions. So in other words there may only be a limited number of rare diseases editing will be available. Just like precision medicine, we can identify somatic mutations in tumors that give indication to the drug the patient is most likely to respond to, or likely to kill most of the tumor. However, just like germline editing, precision oncology is mostly limited by the drugs available and there is still limited knowledge why say genetic features predict some effects for some but not for others. I like the idea of SAGE but putting this into practice is going to be challenging and editing will not be as so widely available as this article portrays it.
Go figure. Our capacity for innovation far outpaces the speed and capacity of regulatory decisional processes.