Exclusive: Dicerna CEO Explains RNA Interference And How It's Used To Treat Rare Genetic Diseases

Ever heard of RNA Interference?

In case you haven’t, Benzinga reached out to Dicerna Pharmaceuticals Inc DRNA’s CEO Douglas M. Fambrough, Ph.D., and asked him to explain how it works.

Silencing Genes

“RNA Interference (RNAI) is a natural process. It is a biological mechanism that every cell in the body has, where the body is able to specifically destroy a particular piece of RNA,” he commenced.

As many of our readers may know, people have all of their genes at the nucleus of every cell in the genome. These genes are “stored as DNA and then read out as pieces of RNA, which are then translated into protein,” the exec explicated. “So, the RNA interference mechanism can be directed to specifically destroy the readout of any particular gene and thus keep that gene turned off.”

Normally, the human body would use RNA interference to regulate genes or to destroy invading viruses. However, what Dicerna does is “redirect this natural mechanism to turn off a particular gene that may be inappropriately active and diseased, and thereby help treat the disease,” Fambrough added.

RNAI Vs. Genetic Engineering

“We don’t do anything to the DNA,” the chief executive moved on to explain. “So, we don’t make any permanent changes. We don’t make any changes that could be passed on to the next generation; we don’t make changes that might -if it goes wrong- cause cancer; we don’t do anything to the DNA, which is that repository of our genetic information. We only affect the readout— This is not genetic engineering.”

RNAI Applications

Benzinga then asked about some applications that Dicerna has for RNA interference.

Fambrough: We are primarily going after rare genetic diseases. These are disease where there is one single gene, which has gone wrong, which is defective [...] This matches very well with our ability to go in and turn off one gene. So, for some of these rare diseases, we can have a really dramatically beneficial effect on the patients.

The first one of these diseases is one called Primary Hyperoxaluria (PH1). This is a disease where, because of the genetic defect, the patient’s liver makes too much of a chemical called oxalate [and] there is nothing the body can do with this oxalate [...] so it is eliminated in the pee.

It is your kidneys that do that filtering and filter the blood to create the urine. [Ultimately], the oxalate ends up destroying the kidneys. So, the patients eventually will need a kidney transplant because their kidneys are shut.

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However, the real problem is that they have a liver that makes too much oxalate. So, unless you want to keep destroying kidneys — and you don’t want to keep doing that, you have to actually do a liver transplant too. So, these patients need a kidney and liver transplant. And meanwhile, while this is happening, this oxalate is depositing around their body and causing a lot of complications.

It is really a very devastating disease, extremely expensive to treat because of all the transplants— and the patients are on dialysis while they are waiting for the transplants.

What we [at Dicerna] can do is turn off the production of oxalate. That’s basically a full treatment for the disease [which leads patients to produce too much oxalate].

We can go in and turn that off. So, it is a perfect match for our technology where we can turn off one specific enzyme and shut down that production of oxalate, which is what the disease is.

A Second Disease In Focus

There is a second rare disease that we haven’t told the world what it is yet, but it is a very similar situation where there is one particular thing that’s wrong and we turn it off.

We’re also doing a program that is really targeted at a far larger population of people who have cholesterol that can’t control, to really turn way down the amount of cholesterol that they make.

And, finally, we’re also using RNA interference to try to develop a treatment for the hepatitis B virus, to try to take the system and turn it into a system that destroys the ability of the virus to infect and replicate.

Interested in knowing more about Dicerna? Check here for Part 2 of this article, where the CEO goes into stock performance, company financials, collaborations, institutional investors and more.