It’s been an exciting several weeks for the field of RNA and DNA editing. Three days after Gail Mandel’s team published their manuscript highlighted in a recent blog, “Editing out Rett Mutations,” researchers at MIT and Harvard also published manuscripts describing alternative methods similarly capable of correcting point mutations that cause Rett Syndrome.
The studies at Harvard and MIT, which were published in two of the most esteemed science journals, Nature and Science, describe modifications to the CRISPR technology platform that enable correction of mutations that cause many genetic diseases including Rett Syndrome. Simply put, these advances allow selective targeting and correction of a single letter in the genetic code with sufficient precision and efficiency to envision profound utility for treatment of humans.
The Nature manuscript describes modifications that allow CRISPR to correct a single letter of DNA without cutting the gene. This advance bypasses a key roadblock for use of CRISPR in non-dividing cells such as the brain. The Science manuscript describes a strategy to edit point mutations in RNA that is similar to the one pioneered in the Mandel lab, but differs in that these scientists employ a new CRISPR-based editing tool discovered in that lab.
These complementary approaches, DNA base editing and RNA base editing, accomplish the same end result by correcting the mutation before the MeCP2 protein is made and both have potential to produce profound efficacy in humans. Both of the new breakthroughs leverage insights of research teams that are at the cutting edge of CRISPR, a technology that enables gene editing. Importantly, these discoveries mark the first time we have the ability to apply this powerful technology to diseases that affect the brain. In Rett Syndrome, this could have profound efficacy as editing would specifically correct the mutation and MeCP2 protein production would be optimized under control of the normal regulatory mechanisms.
It’s important to note that both DNA and RNA editing therapeutics will need to be delivered into the brain using vectors. The vector research ongoing at both AveXis and the RSRT-funded Gene Therapy Consortium will be critical to advancing the DNA and RNA editing into the clinic.
As always, we will continue to closely monitor advances in this fast-moving area of research. We will also leverage the expertise and capabilities of the scientists within our funded scientific consortia to rapidly evaluate the ability of these new technologies to correct the relevant mutations that cause Rett Syndrome.