I’ve Gone All-in on Gene Editing

Something pretty big happened on Monday. Intellia, which is a genome editing company that uses CRISPR to slice up, remove and add DNA segments, announced some pretty amazing results from their Phase 1 trial targeting a rare disease called transthyretin (ATTR) amyloidosis.

ATTR amyloidosis happens because of a mutation to the TTR gene. This mutation makes the liver produce misfolded TTR proteins. These misfolded proteins get into other organs and wreak havoc on them.

With CRISPR/Cas9, Intellia’s therapy targets the gene and basically knocks out the mutation from the strand (this is called a “knock-down”). Without the mutation in the gene, the body stops producing the misfolded proteins and all is well.

From FierceBio: David Lebwohl, M.D., Intellia’s chief medical officer said that the the result was “beyond what we expected.”

These results, it seems to me, are a very big deal. Why? Because this is the first time that the CRISPR/Cas9 system has been used in a trial, inside a human being, to change a gene (called in vivo).

Up until now, if you wanted to change a gene with CRISPR, you had to do it in vitro – which means either taking cells out of the body or using someone else’s cells, slicing and dicing the DNA, and then injecting them back in.

Obviously this is not ideal. It really limits the usefulness. It is much better to be able to administer the therapy into the body and let the work happen there.

And now we have evidence you can do that. A one time treatment and boom – a functional cure to an awful disease.

This is the first time I’ve written about gene editing with CRISPR (I think?) but I have been working on this for months. I’ve read three books on the topic (one of the co-founders of Intellia, Jennifer Doudna, is the main character in the book The Code Breaker, which was a good introductory overview of the sector for me), and have been pouring over brokerage reports and papers on it. I’m still a newbie but starting to get the just of it.

Enough to know that this is a pretty big deal.

For some perspective, this is only a Phase 1 trial, so there’s that. And the target that Intellia chose is a gene that is in the liver – the liver, from my understanding, is a relatively easy target because getting therapies delivered to it migrate there easily.

As a final caveat, one of the big problems with CRISPR is something called off-targeted edits, which is exactly what it sounds like, editing genes somewhere else, and Intellia noted 7 of them in this case. These could be bad or they could be nothing. From what I read we often won’t know if they are a problem until they are a problem.

But even with all these caveats, the big picture is that it worked. In fact, the results were far better than anyone expected.

The thing about in vivo CRISPR therapies is that if they work, they can basically knock out problem genes or replace problems genes or add good genes with a single treatment. Instead of treating symptoms or supressing a problem they are really knocking the problem right out of the body. It really is a game changer.

The obvious thing to do after these results would have been to buy Intellia. So of course, because I am an idiot, I did not do that. It was just up so darn much Monday morning – but of course since Monday it has been up even more.

Instead I bought all the others: CRSP, EDIT and GRPH. CRSP has not really moved since Monday, likely because its been so overbought, but the other two have continued to move up.

Even though these stocks have very high market capitalizations and, of course, no real revenue, I felt that I just had to own them. Literally the only thing that had kept me from these stocks in the past few months was that I kept thinking, if this is just a treatment that is only done in vitro, that is going to be pretty limited application.

But that is no longer the case. I feel like it will take some time for the market to truly catch up to that change.