"Ghosts Of mRNA Past & Present": 6 RNA/LNP Execs Revisit 2024
By Anna Rose Welch, Editorial & Community Director, Advancing RNA
I daresay we’re all familiar with Charles Dickens’ popular seasonal tale, “A Christmas Carol,” in which three ghosts/spirits of the past, present, and future appear to the miserly Ebenezer Scrooge to guide him to redemption.
I acknowledge this is a weird reference to make at the beginning of an article on RNA. But as I reviewed my 2025 outlook conversations with six RNA and/or LNP executives, I couldn’t help but think about the “Ghosts of Christmas Past & Present” — or the “Ghosts of mRNA Past & Present,” if you will — as each executive shared his or her thoughts on the progress we made in 2024. Now, to be clear, all the executives I spoke to were very much alive; there was no channeling of spirits during any of these interviews. (…) But much like “A Christmas Carol” with its emphasis on how the past and present inform the future, I was struck by each executive’s appreciation for where we have been and currently are as an industry, and how these moments in time are already informing mRNA/RNA’s bright future.
Below, I share several snippets from the conversations I had with the following executives:
- Dominik Witzigmann, CEO, NanoVation Therapeutics;
- Guillaume Pfefer, CEO of Sail Biomedicines;
- Benita Nagel, co-founder & CEO, & Albert Kwok, co-founder & CSO, of Nuntius Therapeutics;
- Gopi Shanker, CSO, Beam Therapeutics; and
- Alexander Zehnder, CEO, CureVac
Though the mRNA industry is far from “Scrooge-like” and does not need “redemption,” I think we can agree that each of these perspectives demonstrates where the industry has grown and in what ways this growth continues to raise the bar for us as an industry.
ARW: Pretend you are trapped in an elevator with a poet (a.k.a. me…) who is incredibly curious about the world of RNA (also me). What’s your ‘elevator pitch’ for the state of the mRNA/RNA sector as we near the end of 2024?
A. Zehnder: I recently attended the 2024 mRNA Health Conference in November, and what was impressive to see this year was just how much the field has evolved. Of course, we’re still seeing work being done in infectious diseases, but if you look now, we’re seeing mRNA/RNA technologies entering the oncology, immunology, and rare disease spaces. There are advancements on the delivery side with LNPs and alternative nonviral delivery vehicles. We’re now seeing additional encoding RNA modalities, be it self-amplifying RNA or circular RNA. There’s still this perception that mRNA is a one trick pony. But for me, I think we’re just at the beginning of learning what we can do with this fantastic technology, and the breadth and diversity of RNA research puts us in a good position to make the promise of mRNA a reality. I’m hoping that, in a few years, this diversification in the research will translate into the clinic as well.
G. Pfefer: A few years ago, we witnessed a drug that was developed and scaled to a billion doses in less than a year. Having come from the world of vaccines, this was not something I ever expected to see in my lifetime. Today, we’re keeping the dream of RNA alive by working to make this technology available to patients much more broadly than the first generation of mRNA. Of course, this means addressing some of the challenges that the first-generation players have identified — the first of which is how we can achieve more durable protein expression. The second is delivery: If we can’t deliver the RNA to the right place, we are not going to be able to address significant therapeutic needs.
G. Shanker: There is still a tendency to think about RNA therapies predominantly as a vaccine technology. But after the past year, I’d argue that RNA-based gene editing and base editing has now arrived as a Bona fide modality. Throughout 2024, we’ve seen preclinical and clinical data demonstrating RNA’s potential in gene editing — both ex vivo and in vivo — which I hope means gene editing and base editing can now start to emerge from the sidelines and become a widely recognized application for RNA.
ARW: What have been the most important developments you’ve noted over the past year in the RNA and/or LNP space, and what does this suggest to you about the future of RNA/LNP development?
D. Witzigmann: Post-COVID, we have seen a pivotal shift in how the industry views LNPs. LNPs are much more than “just” excipients; they’re key to overcoming delivery barriers and not as simple to work with as our successes during the pandemic made it seem. While the success of mRNA vaccines brought LNP technology into the spotlight, it also led to some oversimplification. Many companies assumed they could utilize a one-size-fits-all approach for LNPs, especially considering that the first approved LNP product Onpattro shared a similar composition and molar ratio to the COVID vaccines. However, during the last 18 months or so, we’ve seen that biotechs and Big Pharma are more open to collaborating with specialized LNP innovators. Navigating the complex IP landscape and addressing application-specific needs have become key topics. Companies have realized that this one-size-fits-all approach does not work. We need to have what I like to call a “fit-for-purpose” LNP that is customized for specific payloads, target tissues/cells, and routes of administration.
B. Nagel: Over the past year, mRNA-based therapies have delivered impressive clinical results, showing their promise well beyond infectious diseases. For example, BioNTech’s pancreatic cancer vaccine kept 40% of patients cancer-free for at least three years — an extraordinary outcome. With mRNA cancer vaccines on the cusp of commercialization, we expect interest and investment in this field to grow significantly. Advances in gene editing are also promising. Intellia’s Phase 2 mRNA-based CRISPR treatment for hereditary angioedema achieved majority complete responses. These breakthroughs make us incredibly excited for what lies ahead.
Shanker: In August of this year, Beam announced that the FDA cleared the IND for our in vivo base editing program in glycogen storage disease. Obviously, this is a big milestone for our company, but I also think it’s revolutionary for the gene editing/base editing space at large. Not only does an IND grant Beam the ability to do clinical trials in the U.S., but it points to the fact that the FDA has weighed the risk-benefits of in vivo editing. A year or so ago, the FDA was largely conservative and in watch-and-wait mode on in vivo gene editing. But now we have seen both Verve and Intellia progress farther into the clinic, and with our recent IND clearance, we can begin to add more data into the mix. Base editing is now really in the clinic.
ARW: The importance of partnership is typically a common refrain in every conversation I have — whether these partnerships be with venture capitalists, biotechs/Big Pharma companies, and/or regulators. Which areas demand even closer partnerships or more collaboration in the year ahead, and why?
Zehnder: One of the biggest questions I have is how regulators will approach the concept of the platform moving forward. If we look at personalized cancer vaccines, for example, each vaccine will be slightly different because it’s tailored to the genetic makeup of an individual tumor. To make these therapies readily available at a reasonable price and to enable quick and agile development, there will need to be a lot of rethinking and collaboration between the field and especially with regulators because this is still relatively uncharted territory.
Pfefer: In this day and age, nobody can operate, survive, and strive alone. When it comes to developing, manufacturing, and commercializing drugs, we need to be humble and always aware of the fact that we need a village to be successful. In other words, biotech is the ultimate team sport. For Sail in 2025, this means, firstly, continuing the current success of our research-based partnerships with the Cystic Fibrosis Foundation and the Bill & Melinda Gates Foundation to explore the benefits of Endless RNA™ [circular RNA] compared with traditional mRNA in both therapeutics and vaccines. Secondly, we will be determining the right strategic partners for some of Sail’s other programs, potentially including those we are advancing in in vivo CAR-T for autoimmune disease, GLP-1, and rare disease.
Witzigmann: Closer collaboration with clinicians will be key to understanding what is clinically meaningful. Clinicians have invaluable insights into disease-specific challenges and practical administration methods. If we think about all the different forms of delivery beyond systemic administration — for example local administration such as intratumoral injection — we can learn a lot from daily clinical practice. To improve LNP delivery and nucleic acid delivery in general, we need to understand from the clinicians what we need for each disease and how the disease may affect delivery to the target cells.
A. Kwok: I’d really like to see more partnerships between early-stage biotech and big pharma during preclinical phases again. The recent market downturn has shifted the focus toward clinical-stage developments. Many promising novel advanced therapies, such as RNA-based treatments, are still in earlier stages. Advancing these innovations is critical to overcoming the limitations of today’s solutions. Early-stage biotech brings innovative and cutting-edge technologies, while pharma offers extensive resources and robust preclinical and clinical operations. By partnering, both sides can accelerate progress and drive transformative breakthroughs — a win-win that ultimately benefits patients.