Scientists have been working hard to come up with a brand spanking new gene-editing system that can slip genes right into human DNA. Sounds pretty cool, right? This system could potentially help in treating genetic diseases caused by a whole bunch of different mutations. They’ve only tested it out on human cells in a lab so far, but who knows what the future holds? If it turns out to be safe and effective for patients, it could be a game-changer in the world of gene editing.
What’s the deal with this new system, you ask? Well, instead of focusing on fixing a single gene mutation like other gene-editing tools, this bad boy is all about sliding in a working copy of the gene into those cells. Isaac Witte, a smarty-pants doctoral student at Harvard University and co-lead author of the research, explains that many genetic diseases can be caused by a whole slew of mutations in the same gene. Take cystic fibrosis, for example — it can be triggered by over 2,000 different mutations in a specific gene. That’s a lot of mutations to deal with, my friend. Using genome editing to tackle all those mutations can be a real pain in the neck, and it can take forever to get all those approaches approved. So, introducing a fresh gene to make up for the broken one seems like a pretty nifty alternative, don’t you think?
This new gene editor, as described in a report published in the journal Science, allows for these kinds of edits and can pop the new gene right “upstream” of where the broken one is hanging out in human DNA. There’s still a lot of work to be done before this gene editor can be put to use in medical practice, but the researchers are pretty pumped about it. They’ve been directing evolution in the lab to make it all happen. The core of this gene editor comes from bacteria, just like the regular CRISPR systems, but it doesn’t slice and dice DNA like those “molecular scissors” do. Instead, it shuffles large chunks of DNA from one spot to another in a super targeted way. These systems, known as CRISPR-associated transposases (CASTs), have been around since 2017 and let “jumping genes” hop around in the DNA of cells. Cool, right? Well, not really sure why this matters, but these CASTs are pretty handy for gene editing because they don’t make a mess by cutting up the DNA. Regular molecular scissors can cause all sorts of issues when they slice up DNA and make the cell try to patch things up. But not these CASTs — they’re smooth operators.
The team of researchers, led by Samuel Sternberg from Columbia University, decided to make these CASTs more user-friendly for human cells. They started off with a CAST from some bacteria called Pseudoalteromonas, which showed a little bit of activity in human cells in previous studies. Then, they used an experimental method called PACE to speed up the evolution of the CAST. With each round, they tweaked the system a bit more. After a bunch of rounds, they evolved a new CAST that could slip DNA into human cells with 200 times more efficiency than the original. It took a ton of time and generations, but they finally got there. The evolved CAST, lovingly named evoCAST, has 10 key mutations that make it work like a charm in human cells. But it’s not perfect — it works better in some human cells than in others, so they’ve got more work to do. They tested evoCAST on genes that cause diseases like Fanconi anemia, Rett syndrome, and phenylketonuria, and it worked in about 12% to 15% of treated cells. That’s not too shabby, right? Well, who knows how efficient it really needs to be to cure a disease? That’s something they’re gonna have to figure out.
