Gene Therapy Could Be Getting an Upgrade

By Quinn Fucile | Apr 02, 2015 03:12 PM EDT

If you're a repeat reader of this website, then you might be familiar with CRISPR-Cas9. But in case you're new, let's review. We'll call the whole system Cas9 for short, but it's collection of biomolecules including enzymes.

It was originally found in the immune system of bacteria, and how they dealt with viruses. Part of this system is a molecule composed partially of RNA, and this RNA is complimentary to viral DNA. Once the targeting RNA binds to the viral DNA, an enzyme can lock on and chop it up. By isolating these molecules and customizing the targeting RNA, scientists have been able to use this as a very powerful tool. With relative ease, compared to other methods, scientists have been able to remove and add genes to any organism that the system has been attempted on.

This is all very exciting news, and is amazing for the potential of biotechnology research. However, one of the main limitations is that it has mainly been used in research. It's the tool of choice for modifying microbes to experiment on or creating other transgenic organisms. When multicellular organisms are created, it's done so by modifying their very early embryos in vitro. Modifying cells in a petri dish or other culture is much easier than modifying cells inside a living organism. In vitro, scientists have almost complete control of the environment that the cells are in. Tiny holes in cell membranes can be made using electricity, temperature, or chemicals; allowing the Cas system to just drift in.

But this system is so effective and flexible that it could be a booster to gene therapy research. The problem is, current vectors for many gene therapies are simply too small to carry the enzyme and other necessary molecules. That's where this breakthrough comes in, as a result of collaboration between MIT and the Broad Institute. (via EurekaAlert)

This group analyzed 600 bacterial genomes, looking at the sequences that coded for the Cas system. After plenty of work, they found a version of the enzyme that was 25% smaller than the version predominantly being used in research today, but so far it's just as customizable and effective.

This new version is small enough to fit in a adeno-associated virus, a viral vector already being clinically used in gene therapy experiments. As a proof of principle, they knocked out a target gene in adult mice. Other experiments have shown that knocking out this gene reduced bad cholesterol, and overall improved cardiovascular health. One week after the gene therapy, the mice had virtually no sign of the targeted gene and 40% reduced bad cholesterol.

With this success, the new version of Cas9 may become the standard. It opens up the door to gene therapy and many other possibilities where injecting the system into living organisms is desirable. And the researchers aren't even stopping, there's still analyzing the different structures to see how they can further optimize the enzyme for size. 

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