Within our integrated Pharmaceutical Development & Manufacturing framework, our Drug Substance Development teams work seamlessly with the specialized RNA-based Therapy Product Development group to advance coding RNA modalities from concept to manufacturing readiness. We engineer in vitro transcription (IVT) processes, scalable purification, and preformulation strategies that translate into robust, reproducible quality attributes and dependable performance in downstream applications.
Overview of Coding RNA Therapeutics Development
Coding RNA platforms (conventional capped mRNA, self-amplifying RNA (saRNA), and circular coding RNA (circRNA)) enable transient, cell-directed protein expression. Development hinges on harmonizing sequence architecture (5' cap/UTRs, coding region, poly(A) tail), IVT process chemistry, and delivery formulation to achieve potency while controlling innate sensing and degradation pathways. We apply quality-by-design to map critical material attributes (template integrity, cap identity, poly(A) length, modified nucleotide incorporation) and critical process parameters (NTP balance, Mg2+ and pyrophosphatase levels, reaction temperature/time). Orthogonal purification is used to minimize dsRNA and residual DNA template. Analytical development establishes sensitive, stability-indicating methods for identity, purity, and functionality. The outcome is a manufacturable drug substance and drug product strategy aligned with regulatory expectations for RNA quality, consistency, and comparability.
Fig.1 Schematic of coding mRNA architecture showing the Cap 1 structure at the 5' end, 5' untranslated region (5' UTR), coding sequence (CDS), and the 3'poly(A) tail.
Our Services
We provide an end-to-end, development-focused CDMO offering spanning drug substance process development, template and sequence engineering, analytical method development, preformulation, and CMC documentation support.
Coding RNA Drug Substance Process Development Service
We optimize IVT at bench scale and scale-down bioreactors, balancing NTP ratios, capping method (co-transcriptional or enzymatic), and modified nucleotide use. Downstream, we design purification trains (e.g., DNase digestion, TFF, chromatography, cellulose-based dsRNA reduction) to deliver high-integrity, low-impurity RNA. We establish hold-time studies, in-process controls, and material genealogy suitable for tech transfer to GMP manufacturing.
Template & Sequence Engineering Service
We design and produce high-fidelity DNA templates (linearized plasmid or synthetic constructs) and engineer coding sequences for translational efficiency and manufacturability. This includes rational 5'/3' UTR selection, Kozak context, codon usage, GC distribution, poly(A) tail strategy, and structure minimization to reduce abortive transcripts and dsRNA byproducts without over-constraining design space.
Analytical Development & Method Qualification Service
We build phase-appropriate, stability-indicating methods: purity/identity (AEX/HPLC, CE, LC-MS for cap variants where applicable), size and integrity (agarose/Bioanalyzer), dsRNA content (immunoassays/orthogonal LC), residuals (template DNA, proteins, solvents), and potency (cell-based translation or biochemical surrogates). Methods are qualified for accuracy, precision, specificity, and robustness; reference standards and system suitability are defined for reliable lot release and comparability.
Regulatory CMC Documentation Support Service
We author and compile phase-appropriate CMC documentation (e.g., process descriptions, control strategies, method summaries, and stability rationales) consistent with Module 3 expectations for RNA drug substances and products. Our teams align narratives with risk assessments, ensuring clarity and continuity through future lifecycle updates.
Our Coding RNA Therapeutics Development Portfolio
We support mainstream, translatable categories of coding RNA platforms and routinely tailor processes and analytics to each modality. We provide, including but not limited to, development services for the following:
- Capped, polyadenylated mRNA
- Self-amplifying RNA (saRNA)
- Circular coding RNA (circRNA)
- Multicistronic mRNA
- Trans-amplifying RNA systems
- mRNA for secreted or membrane proteins
- mRNA encoding programmable nucleases or polymerases
- …
We integrate sequence engineering, IVT chemistry, purification, and analytics into a coherent CMC strategy for coding RNA platforms. Our development-focused CDMO services reduce risk, accelerate manufacturability, and prepare your program for efficient advancement. Contact us to discuss your goals.
Our products and services are for research use only.
