It's Okay To Be Smart

Cut-and-paste therapy fixes mouse hemophilia!

The assembly of ribbons, beads and string you are looking at represents the 3-D structure of Factor IX protein. Lurking within its intricate, convoluted folds is a biological activity essential to keeping blood inside your body, where it belongs. Factor IX is an important part of the coagulation pathway that allows blood vessels to clot and heal. When this protein is mutated, it leads to hemophilia B. You’ve probably heard of it.

Because this disease is caused by a single gene, it’s been a target for gene therapy for a long time. If we could replace the broken gene with a functional one, we could cure hemophilia instead of just treat it. Well, it looks like that dream may be closer to reality.

“We can rebuild him. We have the technology.”

A team from Philly, working together with a Cali biotech company (it’s nice that they have settled their East Coast/West Coast feuds), have used precision genome editing tools to repair the Factor IX gene in a live mouse. To understand how they did this, remember that a “broken” gene would have mutations in the DNA sequence somewhere, and that we can figure out precisely which bases would need to be changed.

Using a pair of “molecular scissors” called a zinc-finger nuclease, the scientists were first able to create a very specific cut in the DNA at a pre-programmed site inside the Factor IX gene (and nowhere else, hopefully). Then, they pumped the cells with small pieces of DNA containing the correct, healthy sequence. By utilizing that little cut in combination with a piece of DNA containing non-mutated sequence, they were able to literally cut and paste the mutation out. They use the cell’s natural repair machinery to do this, they just trick it in a sense.

Teams have been trying to use “repair DNA” to edit genes for decades, but when it came to moving it outside of the lab, they always had problems with low efficiency or with introducing changes (sometimes dangerous ones) in parts of the genome that they didn’t want to change (like a cancer gene, for instance). These “molecular scissors” are the tool that finally allows them to edit exactly where they want and not introduce changes elsewhere.

It remains to be seen whether the zinc-finger nucleases are as safe and precise as the scientists think that they are, and whether they will be able to program them to cut at the thousands of potential disease mutation sites that we know of. There’s still lots of research to be done, and of course a mouse is not a human.

But we are getting closer.

(Full disclosure/backstory: One of my side projects in grad school has been working on a similar but different gene editing tool, so I have both a soft spot in my heart and a great deal of personal jealousy for these research teams. Sangamo Biosciences, if you’re reading, I’m graduating next year. Let’s talk jobs!)

(via Nature News)