As a specialized CDMO, we integrate end-to-end capabilities across Pharmaceutical Development & Manufacturing › Drug Substance Development › RNA-based Therapy Product Development. We focus on robust CMC packages for non-coding RNA (ncRNA) modalities while prioritizing manufacturability, analytical rigor, and delivery performance.
Overview of Non-Coding RNA Therapeutics Development
Non-coding RNA modalities, such as antisense oligonucleotides (ASOs), small interfering RNA (siRNA), microRNA mimics/inhibitors, and RNA aptamers, rely on precise chemistry, sequence architecture, and delivery systems to achieve intended gene-regulatory outcomes. Development hinges on the interplay among backbone and sugar modifications, conjugation strategies (e.g., ligand-targeting), and nanoparticle-based presentations that safeguard integrity and enable productive cellular uptake.
Fig.1 ASO development workflow.
From a CMC perspective, the major challenges are control of length and sequence identity, stereochemical and linkage consistency, duplex annealing and strand stoichiometry (for siRNA), impurity clearance (shortmers, failure sequences, residual reagents), and formulation stability under real-world storage and distribution conditions. A sound control strategy must connect design attributes to critical quality attributes (CQAs) and validated analytical methods, ensuring the product is reliable, reproducible, and scalable.
Our Services
Our focus is on CMC-driven research and development: design-for-manufacturability, process and analytical method development, stability strategy, and quality-by-design frameworks—culminating in submission-ready documentation.
Sequence & Chemistry Design-for-Manufacturability Service
We translate target-level concepts into manufacturable ncRNA constructs without drifting into discovery. Our chemists recommend sugar and backbone modifications (e.g., 2′-substitutions, phosphorothioate patterns, locked/bridged nucleic acids where appropriate) that balance nuclease resistance, hybridization, and process simplicity. We optimize terminal motifs, overhangs, and annealing regions for siRNA; gapmer versus steric-block designs for ASOs; and minimal-structure, high-affinity architectures for aptamers.
Solid-Phase Oligonucleotide Drug Substance Process Development Service
For ASO and siRNA strands, we build robust solid-phase oligonucleotide synthesis (SPOS) processes: phosphoramidite selection, coupling/oxidation/sulfurization cycles, deprotection/cleavage, and desalting. We define critical process parameters that govern length distribution and linkage integrity, and we develop scalable purification trains (ion-exchange and reverse-phase chromatography, ultrafiltration/diafiltration) with in-process controls. For duplex products, we establish annealing and strand-ratio controls and finalize a DS specification aligned to identity, purity, and residuals.
Conjugation & Targeting Ligand Development Service
We develop and qualify chemistries for ligand-oligo conjugates to enhance tissue targeting and uptake (e.g., triantennary carbohydrate ligands, peptides, or other small-molecule moieties). Scope includes linker selection, orthogonal protection strategies, stoichiometry control, and post-conjugation purification. We build analytical fingerprints (LC–MS, HPLC profiling, intact mass, and ligand quantitation) and demonstrate conjugate stability, minimizing free ligand and unconjugated oligo while maintaining hybridization competence.
Analytical Method Development & Characterization Service
We create a phase-appropriate analytical toolbox tailored to each ncRNA modality. Methods include identity confirmation (intact mass, fragment mapping), purity and length distribution (IP-RP-HPLC, AEX-HPLC, CE), duplex integrity and strand stoichiometry (native methods and UV-melting), residuals (solvents, reagents, inorganic salts), endotoxin/bioburden, and potency-linked hybridization assays. We progress methods through qualification to support specifications and stability-indicating status, and we build method lifecycles with clear system suitability and trending plans.
Stability & Forced-Degradation Strategy Development Service
We map degradation pathways (hydrolysis, depurination, desulfurization, oxidation) through forced-degradation studies and generate stability-indicating methods with defined acceptance criteria. We design accelerated and long-term studies under ICH-aligned conditions, evaluate photostability and freeze–thaw tolerance, and optimize storage temperatures, protective atmospheres, and secondary packaging.
Quality-by-Design (QbD) & CMC Documentation Support Service
We implement QbD principles—defining a target product profile for the modality, identifying CQAs, and mapping them to unit operations, materials, and analytical controls. We assemble comprehensive CMC documentation: process descriptions, control strategies, specifications, method summaries, stability protocols, and comparability frameworks. Our packages are structured to facilitate global filings while remaining modular for future lifecycle changes.
Our Non-Coding RNA Therapeutics Development Portfolio
Our services support widely adopted ncRNA categories:
- Antisense oligonucleotides (ASOs)
- Splice-switching oligonucleotides (SSOs)
- siRNA duplexes
- microRNA mimics & inhibitors (Antagomirs)
- RNA aptamers
- Ligand-conjugated oligonucleotides
- LNP-presented ncRNA
- …
We deliver end-to-end CMC solutions for non-coding RNA modalities, integrating manufacturability-minded design, drug substance development, rigorous analytics, and stability strategy. Engage our team to accelerate high-quality, filing-ready ncRNA products with confidence.
Our products and services are for research use only.
