Specific needs for RNA-based therapeutics require individualized solutions. At Eclipsebio, we offer lab-in-the-loop RNA therapeutic support through our eCOMPASS platform to assist you in any phase of therapeutic development. With eCOMPASS, drug developers iterate through RNA design, prototyping, and characterization until they have the RNA therapeutic and insights they need, with each round of the process resulting in a better drug candidate than the last.  

In this eBlog, we describe what drug developers can expect when onboarding an RNA therapeutic project with eCOMPASS. While this eBlog details the entire lab-in-the-loop platform, drug developers can start or end their process with any step in the cycle. 

Step 1: Design your RNA sequence 

A program requiring sustained, high-level protein expression demands a fundamentally different design than one where a brief, controlled burst is the target. Every RNA therapeutic has a different definition of success, and we start there. Our team works with you upfront to define what your therapeutic needs to achieve, so that every design decision that follows is oriented around your actual target product profile. 

From that foundation, we take your protein sequence into eNAVIGATE, our AI-powered optimization platform. Where most codon optimization tools design for manufacturability alone, eNAVIGATE considers the entire lifecycle of the RNA, including how it will behave in the cell and what therapeutic effect it needs to deliver. Over the course of a typical engagement, the model trains on over 150,000 experimental data points specific to your program, continuously evaluating tradeoffs across key performance dimensions to surface the strongest candidates. 

Before any candidate moves to manufacturing, we validate designs in silico. Our proprietary databases flag predicted assembly risks, cloning challenges, and problematic sequence motifs, including those prone to hydrolysis or recognized by RNA-binding proteins and microRNAs, so every candidate that reaches the bench is built to succeed. 

Step 2: Manufacture a prototype 

Speed matters in early-stage development, which is why we prototype in-house. We take candidate sequences and rapidly produce small-scale prototypes, assembling DNA fragments into plasmids, then driving through bacterial transformation and clone selection. From the verified plasmid template, we perform in vitro transcription to produce your mRNA, incorporating modified nucleotides upon request to support specific stability or immunogenicity requirements. 

We verify every prototype before it moves forward. Nanopore sequencing confirms sequence identity, and Sanger sequencing ensures poly(A) tails are intact. Our experience with difficult sequences means we can reliably prototype constructs that stall other platforms, including linear mRNAs greater than 10 kb. 

Step 3: Characterize your therapeutic 

With prototypes in hand, we move into sequencing-based characterization using our eMERGE platform. This is where the lab-in-the-loop cycle pays off. Rather than simply confirming whether a candidate meets a quality threshold, eMERGE tells us why it is performing the way it is. 

eMERGE generates insights across the critical quality attributes of RNA therapeutics: identity, integrity, stability, potency, purity, and safety. We can locate dsRNA impurities, resolve RNA secondary structure, map hydrolysis hot spots, and identify ribosome stalls or frameshifts all in the context of your protein and target cell type, with single nucleotide resolution.   

What makes this data so actionable is its mechanistic depth. Whether we find a structural element limiting translation efficiency, a dsRNA species affecting innate immune activation, or a stability issue tied to a specific sequence region, those findings feed directly back into eNAVIGATE to inform the next round of design. Each iteration starts smarter than the last. 

After analyzing your samples, we provide an action-ready report detailing what we found and what we recommend. Depending on the results, we move into another design-make-test cycle to further optimize or advance your lead candidate toward the clinic with confidence. Once you have a lead candidate selected, we can pair you with a member of our network of manufacturing partners to perform GMP-like manufacturing and scale-up for preclinical studies. 

Use this cycle as needed 

Depending on your needs, you may only need certain parts of this cycle. You may prefer your in-house manufacturing or already have a prototyped therapeutic and just need to characterize it. No matter what your current stage in the therapeutic lifecycle, eCOMPASS can guide you to the optimal candidate. 

Interested in designing, prototyping, and/or characterizing an RNA therapeutic with eCOMPASS? Contact us today to get started.