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27 Sep 2021

Podcast: Giving genes the silent treatment, with Dicerna Pharmaceuticals

In our latest episode of One Step Ahead – our podcast designed to help future-proof your portfolio – we put the spotlight on Dicerna Pharmaceuticals, an innovator in gene-based medicine and a holding of our Disruptive Technology ETF.

Dicerna Pharmaceuticals is a Massachusetts based biopharmaceutical company specialised in “RNA interference” (RNAi), a ground-breaking technique that can target and silence certain disease-causing genes in order to restore patients’ health, and improve their quality of life.

To help us understand RNAi, and what the future of gene-based medicine holds for us, we spoke to Douglas Fambrough, Ph.D., Dicerna’s CEO and President. From kidney-related disease to neurological disorders – and potentially even alcohol use disorder – he asserts that gene-based medicines have the potential to be a safe and effective approach to treating disease. According to Dr. Fambrough, we’re at the early stages of a “big bang” for gene-based medicine, and RNAi is just one of many disruptive technologies set to change the future of healthcare.​

Diana

Douglas Fambrough     
President and CEO, 

Dicerna Pharmaceuticals

Below are a few edited highlights from the episode. You can listen to the full episode on your favourite podcast platform (including Spotify, Apple Podcasts, Google Podcasts, Stitcher) or right here on the Lyxor ETF website:

Libby: Doug, the phrase “we interfere” is repeated in many places on Dicerna’s website. Can you explain to our listeners what it is you mean by that?

Douglas: I'd be happy to explain. We intended that phrase to be a little startling and a little unusual to capture attention. At Dicerna, we interfere with disease. Disease processes divert people from their normal life in terrible ways, and we want to interfere with the ability of the disease to do that.

The phrase plays off the name of the technology we use, which is called RNA interference. And so for those technically in the know, it's a play on the word ‘interfere’, but it's designed to sort of grab your attention and show that we're interfering with disease. That's what we do to try and restore health.

Libby: There's been a lot of buzz around advances in healthcare innovation and genomics, with terminology like mRNA, gene therapy, and gene editing all making headlines, particularly with Covid-19 vaccines. Would you mind briefly explaining the differences between these concepts, and how Dicerna’s gene silencing approach is different?

Douglas: I think we all know the machinery of our body that operates every day – it’s primarily made of proteins. (…) But then we have a genetic code, or the ‘instruction set’ that encodes all the directions to make all of these proteins. And you can think of our genome – this genetic instruction set – as an enormous recipe book with 20 to 30 thousand pages and a recipe on each page to make a protein.

Now, if you think of that as a recipe book, and each protein is maybe a dish that's made, you could never bring a book that big to the kitchen counter. So you have to make a copy of a page and bring it over to the counter in order to make the protein. Traditionally drugs were made to interfere with the actual machinery, to interact with the proteins that are made.

But all of the technologies you mentioned are about instead looking at the genetic instruction set, and they either work on that big recipe book or on the copy that's made of the particular page. (…)

  • mRNA is the copy that's made of one page of the recipe book of the genome to encode for a specific protein. What mRNA companies do is they provide a copy from the outside. In the case of the vaccines, they provide a copy of a viral protein that your body then makes into the viral protein so your immune system can recognise it. Now, it's not the full virus, so it's not infectious. But this is good for when a patient is missing a gene. You can put the copy for that gene back in so the protein could be made. Or if you need more of the activity of one gene, if you’re low on a hormone or something, you can put in a copy and make more of the hormone.

  • What we do is the flip side of that. If you have too much of one of the genes, RNA interference disrupts the ability to read out the copy of the gene. In fact, sometimes it's called gene silencing. It prevents the gene from being made into the protein. A lot of common diseases, whether cardiovascular, acid stomach, autoimmune, or inflammatory diseases – they involve where there's too much of a biological process going on. (…) 

The other technologies you mentioned [gene therapy, gene editing] operate on the instruction set itself. Now, the instruction set is permanent; the copies are transitory. So when you intervene with the copies, with mRNA or RNA interference, it lasts for a little while, then it fades away and you have to give the drug again. But technologies that work on the instruction set – they’re lifelong and permanent, so one would want to be very careful.

  • Gene therapy, as it's normally called, is basically putting a new page into the genome. And so if one of the pages is missing or just damaged so that it doesn't function properly, you can put a brand new page and an extra page that replaces the defective page. This is particularly good for genetic diseases where a gene is missing or someone inherits a defective copy of a gene from both parents. (…)

  • The last technology, which is the newest and youngest and has no approved products today unlike the other three, is gene editing. That is going in and kind of literally editing the words on the individual pages. One simple way to edit is just to kind of erase stuff and take a page and break it. That's a bit like RNA interference in that you turn the gene off by breaking it at the instruction set level. And that would be lifelong. (…) And the other way to do it, which is a little harder and a little earlier in the technology development process, is actually fix a mistake. So take a page that was incorrectly written and make it the proper code again. (…)

Libby: What is the potential for Dicerna to treat diseases outside of the liver? ​

Douglas: The liver for a variety of reasons is the easiest tissue to do RNA interference in. But having figured out how to make it work in liver and optimise it in liver, that really taught us how we could modify the technology in fairly subtle ways in order to get to other tissues in the body, such as lung tissue, fat tissue, and tissues or cells that are part of the immune system. And that opens up a huge variety of indications.

Also, the central nervous system for diseases like chronic pain or neurodegenerative diseases like Alzheimer's or Parkinson's are far more applications of the technology than Dicerna could do on our own.

And that's why we have collaborations with companies like Roche and Eli Lilly and Novo Nordisk to move into these other therapeutic areas, some of which are very, very large and we couldn't do on our own. For example, the hepatitis B virus with hundreds of millions of patients globally – we're working with Roche on that programme, a large global multinational with global reach. 

Catch up on the rest of the conversation in the full episode of One Step Ahead.

This episode contains forward-looking statements and actual results may be materially different; see “Risk Factors” under Dicerna’s latest SEC filings. 


Relevant ETFs

At the time of this podcast recording, Dicerna Pharmaceuticals was a holding in our SFDR 8 compliant Lyxor MSCI Disruptive Technology ESG Filtered (DR) UCITS ETF (Bloomberg ticker: UNIC).

Swiss healthcare giant Roche, with which Dicerna has partnered on an RNAi therapeutic for the treatment of the hepatitis B virus, is also a holding of our Disruptive Technology ETF.

Learn more about our Thematic ETFs​

This podcast is for informational purposes only, and should not be taken as investment advice and/or an offer to buy financial products. Lyxor International Asset Management, holding the brand Lyxor ETF, does not in any way endorse or promote any companies or securities mentioned in this show. The opinions expressed at the time of recording do not necessarily reflect the views of Lyxor ETF or its parent company, Societe Generale, and may vary from time to time.

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