Money In The Bank: Why 2025's Setbacks Were The Foundation RNA Needed
By Anna Rose Welch, Editorial & Community Director, Advancing RNA
Oh, 2025. Need I say more?
That’s obviously a trick question. For those of you who have followed my writings in the past, you will know that I always have a lot more to say than just two words.
Every year at this time, I try to capture what I saw as some of the most significant developments of the past year for the industry and for yours truly at Advancing RNA.
As we head into January, Advancing RNA will be celebrating its second birthday, and we spent 2025 spreading our wings. We were onsite learning about enzymatic ligation at TIDES US and playing “The Price Is… Sort of, Almost, Not Quite Right!” at the mRNA Therapeutics Summit. Picasso became the industry’s idol when I declared him as such during my keynote address at the CASSS mRNA Symposium, and I/we took to the stage to moderate panels at both RNA Leaders and the AMM Ascent meeting. In our “down time,” we hosted 6 Advancing RNA Live panel discussions which, if you missed them, can be streamed for free here. But perhaps the most exciting news was that we grew our numbers by one with the addition of my partner in crime, Advancing RNA’s own Michael Soloway who is looking at you — yes, you! — in the hopes that you’ll be our next expert contributor. (You can email him here for more information…)
At a 1,000-foot-level, 2025 was a year of incredibly high-highs and some low-lows for the RNA industry. Though we could’ve done without the lows, I’d argue that they were and remain an important part of our journey toward a mature industry. After all, without them, there would be no pressure for us to improve and, dear readers, there is still so much room for us to improve.
Throughout the year, you likely noted several big headline-breaking news items in the RNA space, whether it be the success of dosing Baby KJ with an mRNA-based personalized gene editing therapy; the ongoing policy upheavals in the US that has put the mRNA industry into crisis communications mode; and the big Big Pharma platform deals in the mRNA and oligo space that were reminiscent of the days of the pandemic. As you can imagine, these events were just some of the ones my executive 2026 Outlook articles touched upon in the past few weeks (Part 1; Part 2; & Part 3 can be found here!)
Beyond these headlines, I saw 2025 as a year that was foundational for our efforts to learn more about the biology and function of our products. However, in particular, there were two developments that encapsulated the trials, tribulations, and ultimately the success of an industry that is doing its damnedest to answer one of the biggest questions facing us: “Why RNA?”
Learning From The “Trials” (& Tribulations) Of 2025
All things considered, 2025 was a bit of a “mixed bag” for clinical data — particularly on the therapeutics side.
On the one hand, we had some disappointments in the mRNA sector.
- Intellia announced in October that it was pausing patient dosing/screening following a death in the trial for its ATTR gene editing candidate.
- Arcturus Therapeutics announced some less than ideal results for its first saRNA therapeutic candidate in cystic fibrosis. Though the treatment was safe and well tolerated, it also did not demonstrate meaningful improvement in forced expiratory volume in one second (FEV1).
Not even the more mature oligo space was spared some knocks on the head, perhaps the most prominent being the news out of Korro Bio.
- Korro Bio’s lead candidate, an RNA-editor, didn’t produce the levels of protein in humans that was anticipated based on preclinical results.
- As the press release indicated, we were also reminded that delivery remains a core issue of ours, with the company now pivoting to a GalNAc-based delivery strategy.
You may be wondering why, out of all the possible positive developments (and data!) of 2025, I chose instead to pick at some of our not-quite-yet healed wounds. But there’s a method behind my madness. My ballet teacher often tells me when I take a step back in my training or do a less advanced version of a move that it is all “money in the bank” in building the underlying foundation needed to execute more successfully in the future.
It goes without saying that we and our patients never want to see disappointing data. But I see 2025 as a significant year because we — particularly the mRNA industry — started to figure out the biological complexity of this modality, the therapeutic mechanisms of which, to date, have arguably been overly simplified. Though we would much prefer to see all our drug candidates work out, understanding why our products didn’t work is just as valuable as learning why they do work. These pitfalls help us as an industry and regulators pose better, more informed questions for current and future products in pipelines.
For a great example of this level of inquiry, look no farther than this incredible article presenting an in-depth and balanced look into current research, potential adverse events, and lingering questions the death in Intellia’s trial raises for the CRISPR-based space as a whole. Though there were several questions posed throughout the article, I was drawn to a question around which “component” of the therapy was potentially responsible, be it the gRNA, the LNP, or the CRISPR construct. Such a question highlights the complexity we’ve only just started to recognize in the world of platform technologies — a designation of which we dream for some of our RNA constructs. In fact, please note, though it didn’t occur in the mRNA field, this year marked the first award and revocation of a Platform designation from the FDA (Sarepta’s AAV gene therapy). Though it goes without saying that our molecules are complicated “beings,” 2025 really served as a reminder that there remains a lot yet to learn about mechanisms of action and their clinical impacts across the ATMP space.
The Right RNA for the Job: Answering the "Why, When, and How"
When I jumped into the RNA space shortly after the approval of the COVID vaccines, I often asked executives what a mature industry would look like. And ladies and gentlemen, though 2025 wasn’t our greatest year, there were still a few markers that showcased we’re on the right path in both the mRNA and oligo world.
Maturity will likely mean something different to everyone; but there was one specific way in which I saw increasing maturity show up, if you will: In our increasingly finer-tuned understanding of how our different RNA molecules can function/compete — not just against other modalities, but against each other. As I’ve written in the past, an important question we need to answer as a sector in general is “why an RNA therapeutic?” But in 2025, we also started to pose the question: “Why this type of RNA therapeutic?
For example, we saw this for starters in the vaccine space. As this LinkedIn post beautifully articulates, we’re starting to confirm the ways in which mRNA is “biologically misaligned” to certain indications — for example, those that require tissue-resident memory T-cell induction. (This was nicely reflected in Moderna’s decision to pull the plug on HSV, shingles, and CMV candidates, while Pfizer saw success against a much more “fluid” pathogen — Influenza A.)
Likewise, 2025 also saw the approval of Arrowhead’s siRNA candidate Redemplo for Familial Chylomicronemia Syndrome (FCS). But, interestingly enough, as this LinkedIn post nicely summarizes, this approval also pits the siRNA up against a member of its own RNA family: an ASO known as Tryngolza. Now, this isn’t the first time an siRNA has gone up against an ASO — the ATTR indication has a few siRNA and ASO drug candidates in its treatment ranks. But this was just another data point establishing 2025 — and the upcoming 2026 — as years in which we start establishing a more nuanced understanding of the clinical thresholds of our products.
As the oligo space nicely demonstrates to the mRNA side of the industry, the game doesn’t end with a regulatory approval; how that molecules performs next to or competes against its RNA, biologics, and/or small molecule peers, is another way we as an industry continue to fine tune the all-important understanding of the “why, when, and how” of an RNA therapeutic.