I think that what is so exciting about the future is that we cannot even imagine or comprehend some of the scientific advances. A major area of interest is inheritable diseases and embryos. In some cases the only way to cure some of these inheritable diseases is for them not to occur in the first place. CRISPR, a gene-editing technique has gain a lot of popularity and also some controversy. A new method called base editor technique is similar to CRISPR, but directly makes changes to a targeted site in DNA without any of the cutting. The base editor is a RNA-protein complex. Since many genetic diseases are caused by single point mutations the precision of base editor technique will be more effective. This technique was recently used to correct a gene mutation in human embryos linked to beta thalassemia. The diseases leads to a reduction of red blood cells ultimately leading to organ dysfunction/failure.
In order to have embryos with beta thalassemia, skin fibroblast cells from a patient homozygous for the mutation were collected. Then nuclear transfer embryos were constructed by fusing skin fibroblast with the enucleated in vitro matured oocytes. There were two base editors used, BE2 and BE3, with BE3 showing higher editing efficiency.Therefore, BE3 was used on the embryos. Over 23% of the embryos were fixed using the base editor method, leaving over 75% for more research and improvement.
Although these methods are controversial they will make a big difference on how science deals with genetic disorders. I think that if we have the opportunity to make a human not have to endure the pain that comes along with some of these genetic disorders, then that is what we have to do ethically.
https://link.springer.com/article/10.1007/s13238-017-0475-6
Thanks for the post, Jummy! CRISPR is a very fascinating tool that is expanding in its applications. In its natural form, the Cas9 protein is able to make 2 cuts in DNA or RNA at a location specified by its sgRNA. CRISPR has been modified to allow other implementations of this tool. It was interesting to see how this article tested out the effectivity of a dCas9 system (deactivated catalytic cleavage in both domains) versus an nCas9 (nickase) system that has one active cleavage domain and one inactivated. An important aspect of this design is that they used mRNA to create a transient transfection. A stable lentiviral transduction leads to a stable integration and can introduce other complications depending on whether the integration disrupted a gene, regulatory region, or “junk” DNA. I use this tool at my immunology lab at Anschutz and so I can recognize the benefits in a research setting. When it comes to gene-editing in human embryos there’s a huge ethical component as you mentioned. I agree with you that it’s ethical to allow editing for serious genetic disorders. It gets trickier with mental illnesses or with traits that are under less selection pressure such as aesthetics. We are a while off from having this be a widely used and accepted therapy due to ethical reasons as well as financial, and until that time, hopefully, we will acquire a better understanding of its medical relevance.
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