Inside Terrain’s Design Suite (or, Why predictable mRNA design is so damn hard and how we do it anyway)

TLDR: Most design tools stop at codons. Ours doesn’t.

At Terrain, we've built our design suite to tackle the entire sequence head-on, with a singular focus on predictably engineering mRNA sequences that deliver superior performance for your therapeutic goals.

‍

Why Codon Optimization Isn’t Enough

Traditional approaches to mRNA design often rely on standardized codon optimization tools that only look at the ORF and treat it in isolation, ignoring the other components of the RNA. These approaches fail to account for the complex interplay between different regions of the mRNA molecule and how they collectively impact therapeutic outcomes.

Terrain doesn’t treat mRNA like a list of spare parts to bolt together. We treat it like the complete, integrated system that it is. Rather than viewing the 5' UTR, coding sequence, 3' UTR, and poly A tail as independent entities, we know that changes in one region can profoundly affect the behavior of the entire molecule.

‍

Start with a Comprehensive Design Review

Every successful mRNA sequence begins with our Comprehensive Design Review. This isn't just a formality — it's where we chart a course to hit your goals.

During these conversations, we dive deep into your specific program requirements, therapeutic goals, and biological context. You bring your disease biology expertise and therapeutic targets; we bring our understanding of mRNA sequence design. Together, we identify the key challenges and opportunities unique to your program.

As one of our partners shared after a design review: "Thank you for understanding me. I feel so much better now!" This mutual understanding forms a foundation for successful sequence designs, and ultimately for successful programs.

‍

One of the most powerful aspects of our design stack is its ability to generate improved sequences even when you have limited or no functional data.

‍

Our Design Approach: Whether You Have Data or Not, We’ve Got You

Starting Point 1: Physics-based Modeling using Terrain’s Functional Data (No Partner Data Needed) 

No data? No problem. One of the most powerful aspects of our design stack is its ability to generate improved sequences even when you have limited or no functional data.

For teams just starting out or pivoting to a new therapeutic target (or when you want to move fast and can’t wait for your team to approve a data share), we leverage sophisticated physics-based modeling to simulate and improve your sequence. Our toolkit evaluates:

• Optimal ensemble of secondary structures to achieve a more favorable Boltzmann distribution for improved in-vial and in-cell stability
• Optimal codon selection, considering tissue-specificity and tRNA abundance, for improved expression
• Co-translational folding of protein subdomains to avoid kinetic traps
• Problematic motifs that affect immunogenicity and manufacturability

Even without functional data from you, our design tools routinely improve the performance of the underlying sequence. 

Starting Point 2: Therapeutic Optimization using Partner Data

Once we have functional data (from testing our initial designs or from your existing work), we can start a tailored optimization campaign.

Leveraging active learning, we intelligently nominate new sequences for testing based on real-world performance data. This iterative process allows us to fine-tune sequences to meet your specific therapeutic objectives, whether that's maximizing expression, extending duration, reducing immunogenicity, or achieving the perfect balance between multiple attributes.

‍

We Design for Therapeutic Performance and Manufacturability

Unlike approaches that focus solely on theoretical expression levels, our design services simultaneously consider both therapeutic attributes and practical manufacturability concerns.

This dual focus ensures that your sequences not only perform well in controlled lab settings but can also be reliably produced at scale for clinical applications. We explicitly design and build sequences that won’t break downstream: avoiding restriction enzyme sites, T7 terminator sequences, and other elements that can create manufacturing challenges.

And, designing for manufacturing enables Terrain to build your sequences fast. We build faster and more reliably than every other RNA provider. We can deliver high performing sequences in weeks not months

‍

Our design suite doesn't just aim to make your sequence better in isolation; it aims to make your entire therapeutic program more successful

‍

The Terrain Way

What truly sets our approach apart is our commitment to holistic, integrated design. We understand that the "optimal" sequence isn't about maximizing a single parameter – it's about finding the right balance of attributes for your specific therapeutic objectives.

Our design suite doesn't just aim to make your sequence better in isolation; it aims to make your entire therapeutic program more successful by providing mRNA that behaves predictably and can be tuned to your precise needs.

Whether you're developing vaccines, gene therapies, or protein replacement therapies, our team can help you engineer mRNA sequences that deliver superior performance, manufacturing consistency, and ultimately, better patient outcomes.

Ready to stop guessing and start engineering your mRNA therapeutic? Let’s talk. One conversation could change how you think about mRNA design.