mRNA UTR design

From Generic to Smart: It’s Time to Rethink mRNA UTRs

by Serena Marletta
2 min read
Jun 13, 2025 9:30:08 AM
In a nutshell

From default to deliberate

Generalist UTRs helped mRNA scale fast—but today’s therapies need more than broad expression. This post explores how rethinking UTRs as tunable, tissue-aware modules can unlock smarter, safer mRNA design.

mRNA Goes Mainstream

When COVID-19 swept the globe, something remarkable happened in the biotech world: mRNA stepped out of textbooks and labs and into the spotlight. In just a few months, it became the core of the world’s first large-scale clinical application—SARS-CoV-2 vaccines.

The pandemic eventually receded, but it left behind something transformative: the realization that mRNA is more than a vaccine scaffold—it’s a versatile therapeutic platform. Today, its potential reaches far beyond infectious diseases—mRNA is being explored for protein replacement therapies, cancer immunotherapies like onco-vaccines, gene editing tools, and ex vivo cell engineering.

Not All mRNAs Are Created Equal

The urgency to bring mRNA vaccines to market at unprecedented scale sparked a burst of innovation. Key chemical components like modified nucleotides and capping reagents rapidly evolved—just think of the rise of CleanCap.
But not all mRNA components evolved at the same pace. Some biological design elements were inherited from the past, borrowed from decades-old studies. Case in point: the untranslated regions (UTRs).
To streamline development, developers widely adopted UTRs from hemoglobin mRNAs—most notably those from human, mouse, or rabbit transcripts—well-characterized models used historically to study mRNA regulation and translational control. These UTRs became the de facto standard in the field—not because they were optimal, but because they were available, validated, and “good enough” for an emergency.

stylized_mrna_rotating

Generalist UTRs: Safe Choice, Missed Opportunity

Beyond globin-derived UTRs, even synthetic UTRs used in clinical vaccines are often evolved from well-characterized biological sequences derived from genes that are both highly and ubiquitously expressed. While optimized, they still tend to function as universal elements.

These vaccine-era UTRs are what we call generalist UTRs: they support broad, unspecific expression across all tissues reached by the delivery vehicle. But now that mRNA applications are diversifying, shouldn’t our design choices evolve, too?

Therapeutic goals differ. Tissue distribution needs vary drastically between a prophylactic vaccine and an onco-vaccine, or between systemic immunization and a therapeutic requiring targeted protein expression. The idea that a single UTR combination could fit all these use cases doesn’t just feel inadequate—it represents a missed opportunity.

 

Today, precision medicine calls for precision design.
And that includes the mRNA blueprint itself.

UTRs as Fast, Flexible Precision Tools

At Officinae Bio, we see UTRs as programmable modules—not placeholders. As experts in UTR design, we know firsthand how much they can impact mRNA stability, translational efficiency, and, crucially, tissue- and cell-specific expression.

Much attention today is rightly focused on targeted delivery systems. We fully support that effort. But in parallel, we advocate for a complementary—and more immediately actionable—strategy: using custom UTRs designed to preferentially drive expression in a specific organ or cell type, even with non-targeted delivery. In other words, we fine-tune what happens after the mRNA arrives.

With this approach, the same biodistribution can result in distinct expression patterns, simply by altering the untranslated regions. That’s the power—and the elegance—of biological control.

UTRs Aren’t Just Passive Passengers

We often refer to them as “untranslated,” but UTRs are far from silent. They’re subtle but powerful regulators of when, where, and how much a gene is expressed.

They deserve to be deliberately chosen, not inherited by default. In fact, by continuing to rely on generalist UTRs, we’re leaving on the table one of the most accessible — and fastest, from a regulatory perspective — levers for increasing the specificity, tunability, and safety of mRNA-based medicines.

 

If we’re already optimizing every other aspect of mRNA design, why are we still settling for universal UTRs?
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