The remarkable promise of oligonucleotide-based modalities for targeted biological pathway modulation demands equally sophisticated development and manufacturing capabilities. As a leader in complex therapeutic manufacturing, we provide comprehensive contract development and manufacturing organization (CDMO) services specifically tailored for oligonucleotides. Our integrated solutions bridge the gap from discovery to manufacturing. Explore our broader capabilities in CDMO Solutions and specialized support for advanced modalities like Precision Therapeutics CDMO Solutions.
Overview of Oligonucleotide CDMO Solutions
Oligonucleotide therapeutics, encompassing antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), aptamers, and other novel structures, represent a rapidly expanding class of molecules with unique mechanisms of action. Their development and manufacturing present distinct challenges compared to traditional small molecules or biologics. These include complex synthetic chemistry, demanding purification requirements, susceptibility to enzymatic degradation, and stringent analytical characterization needs. Our specialized oligonucleotide CDMO solutions are engineered to navigate these complexities. We offer end-to-end support, leveraging deep expertise in solid-phase oligonucleotide synthesis (SPOS), purification technologies (HPLC, UF/DF), chemical modifications (e.g., phosphorothioates, 2'-OMe, 2'-F, GalNAc conjugates), and formulation development. This integrated approach accelerates timelines and mitigates risks inherent in oligonucleotide program progression.
Our Comprehensive Oligonucleotide CDMO Services
We deliver a full spectrum of services designed to advance oligonucleotide candidates efficiently and reliably from concept to patient.
Sequence Design & Optimization Support
While sequence design originates with the client, we provide critical analytical and manufacturing feasibility assessments early in the design phase. Our expertise in structure-activity relationships (SAR) for various oligonucleotide classes allows us to advise on modification patterns (backbone, sugar, nucleobase) that optimize stability, efficacy, and manufacturability. We evaluate potential synthesis challenges, purification hurdles, and stability implications of novel sequences or complex conjugates (e.g., peptides, lipids, GalNAc), enabling smarter design choices that streamline downstream development.
Process Development & Scale-Up
- Synthesis Development: We optimize solid-phase synthesis processes for robustness, yield, and purity at every scale – from milligrams for research to multi-kilogram commercial batches. This includes the development of efficient coupling/deprotection cycles, handling of sensitive modifications, and strategies for minimizing deletion sequences and failure sequences.
- Purification Development: Developing highly selective and scalable purification methods is paramount. We employ advanced chromatographic techniques (IEX, RP-HPLC) and tangential flow filtration (TFF) to achieve stringent purity specifications, removing critical impurities like shortmers, longmers, and structurally related variants. Process development focuses on yield optimization and reproducibility.
- Conjugation & Modification: We develop and optimize robust processes for site-specific conjugation (e.g., GalNAc for hepatic targeting, cholesterol, PEG) and complex chemical modifications performed post-synthesis, ensuring consistency and purity of the final active pharmaceutical ingredient (API).
- Scale-Up Strategy: Our experienced engineers design and execute seamless scale-up strategies, transferring processes from lab-scale synthesizers to robust GMP manufacturing platforms, mitigating risks associated with increased batch size.
Analytical Development & Characterization
Establishing a comprehensive analytical control strategy is critical. We develop, qualify, and validate state-of-the-art analytical methods for identity (MS, sequencing), purity (HPLC, CE), potency (cell-based or biochemical assays), impurities (related substances, process residuals), physico-chemical properties (osmolality, pH, sub-visible particles), structural elucidation and forced degradation studies.
cGMP Manufacturing
We operate dedicated, state-of-the-art facilities equipped with automated synthesizers and purification systems designed for oligonucleotide production under stringent cGMP conditions. Our capabilities encompass:
- Drug Substance (DS): Synthesis, deprotection, cleavage, purification (chromatography, UF/DF), lyophilization (if required), and comprehensive quality control release testing.
- Drug Product (DP):We perform formulation development (solution, lyophilized powder) and aseptic fill-finish (vials, pre-filled syringes) including secondary packaging and labeling. We handle complex sterile liquid and lyophilized oligonucleotide products.
Frequently Asked Questions
Q1: What are the key challenges your CDMO specializes in overcoming for oligonucleotide manufacturing?
We excel in addressing the core complexities: efficient synthesis and purification of long or heavily modified sequences, precise control over critical quality attributes (CQAs) like impurity profiles, developing stable formulations (especially for liquid products), and establishing highly sensitive and specific analytical methods.
Q2: Can you handle complex oligonucleotide conjugates (e.g., GalNAc-siRNA)?
Absolutely. We possess significant expertise in developing and manufacturing conjugated oligonucleotides, including GalNAc-siRNAs, cholesterol conjugates, peptide conjugates, and PEGylated constructs. This encompasses conjugation chemistry development and optimization, purification of the conjugated species from unconjugated material and side products, and analytical characterization specific to the conjugate.
Our products and services are for research use only.
