Mobile genetic elements such as CAST provide an idea of the coding potential of nature for genome manipulation. It is in the spirit of a revolutionary gene editing tool: evoCAST. The concept was born in the scientific community among researchers at the Broad Institute and Columbia University, and evoCAST has the potential to redefine the future of genetic therapies by allowing the precise insertion of full genes into human DNA.
The evoCAST system mimics the natural CRISPR-associated transposase (CAST) process, a method in which genes “hop” to new positions in bacterial genomes. While CRISPR-Cas systems, or “molecular scissors,” are excellent at being precise but generally not precise enough to have a wholesale effect, viral vectors are able to place whole genes but randomly, with possible subsequent undesirable mutation and immune reaction. evoCAST takes advantage of these methods available, but with fewer drawbacks.
The benefit of evoCAST is that it has the ability to generate blocks of DNA of considerable size without causing double-stranded breaks in the genome. This reduces the likelihood of uncontrolled genomic alteration to a great extent, a boon in disease treatment. The efficiency of the system is another gem. In a process known as Phage-Assisted Continuous Evolution (PACE), scientists recorded maximum CAST element evolution rates of 30% at many genomic positions. That is more than 400-fold greater than for the native CAST system.
The possibilities for using evoCAST are endless. For cystic fibrosis and hemophilia, two genetic diseases resulting from thousands of different mutations of a single gene, evoCAST is the solution. Rather than having to create thousands of cures for each mutation, evoCAST could provide us with a single cure that inserts the whole, complete gene into the patient’s genome. It would be simpler, and gene therapy would be more common and feasible.
In addition to the treatment of genetic disease, evoCAST is also potentially useful for a variety of other clinical and research applications. It can potentially facilitate the production of CAR T-cell therapeutics to treat cancer, promote regenerative medicine, and improve the generation of transgenic cell lines and model organisms for biomedical research. The cross-generalizability of the system to other human cell types, such as primary fibroblasts, is indicative of its general utility.
But much still needs to be achieved. Possibly the most daunting task is getting evoCAST and all its genetic data into a cell or target tissue. As Sternberg explained, “That’s a challenge that many of us in the field are facing.” But despite such challenges for all of them, the evoCAST system is a revolutionary step forward in genome editing technology. Scientists are attempting to fine-tune the system, making it even better and more practical in its uses. The development of evoCAST is a gene editing technology breakthrough.
By leveraging CRISPR’s programmability, combined with the capacity to deliver transposases, and evolving them in an iterative fashion, scientists have created a highly versatile and highly specific tool. As gene therapy comes into being, innovations such as evoCAST bring us closer to the day that once incurable genetic disease is treated by a single custom regime. The promise of evoCAST to transform genetic medicine is vast, and the research community holds its breath in expectation to witness what the future holds for it.
