The evolution of therapeutic oligonucleotides, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and aptamers, has revolutionized the treatment of previously "undruggable" genetic targets. However, their clinical application is frequently hindered by rapid renal clearance, susceptibility to nuclease degradation, and potential immunogenicity. At CD BioGlyco, we address these challenges through our specialized PEG-therapeutic oligonucleotide delivery service.
Polyethylene glycol (PEG) conjugation is a gold-standard technology that creates a protective hydration shell around the nucleic acid cargo. This modification significantly increases the hydrodynamic radius of the molecule, effectively bypassing glomerular filtration in the kidneys and extending the circulation half-life. Furthermore, the "stealth" properties of PEG minimize non-specific protein adsorption and unwanted immune recognition, ensuring that the therapeutic payload reaches its intended site of action with higher efficiency and stability. Leveraging decades of expertise in carbohydrate and polymer chemistry, CD BioGlyco provides a comprehensive platform for the design, synthesis, and characterization of PEG-oligonucleotide conjugates tailored to the specific needs of modern drug discovery.
As a pivotal component of our therapeutic nucleic acid development platform, the therapeutic oligonucleotide delivery service at CD BioGlyco is designed to support the entire lifecycle of therapeutic development. We provide specialized PEGylation strategies for a wide variety of nucleic acid modalities:
Our service covers everything from initial screening studies to optimize conjugation density to pilot-scale production for preclinical research. We ensure that every PEGylated product undergoes rigorous purification and characterization to meet the stringent requirements of pharmaceutical development.
We begin with a detailed discussion to understand your oligonucleotide sequence and therapeutic goals. Our experts recommend the optimal PEG molecular weight, architecture, and conjugation site.
We synthesize the target oligonucleotide with the necessary reactive handles (e.g., amino-C6 or thiol-C6) at the specified terminus using high-fidelity solid-phase synthesis.
The modified oligonucleotide is reacted with activated PEG derivatives under optimized conditions (buffer, pH, and temperature) to achieve a high degree of substitution while maintaining bioactivity.
Using techniques such as ion-exchange chromatography (IEC) or size-exclusion chromatography (SEC), we separate the PEG-oligonucleotide conjugate from unreacted reagents and byproducts to ensure maximum purity.
The final product is analyzed using liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and high-performance liquid chromatography (HPLC) to verify molecular weight, purity, and structure.
We perform stability assays in serum or hybridization assays to confirm that the PEGylation has not negatively impacted the functional properties of the oligonucleotide. A detailed final report is provided.
Oncology Research
The enhanced permeation and retention (EPR) effect facilitated by PEGylation allows for better accumulation in solid tumors, improving gene-silencing efficiency and reducing systemic toxicity.
Rare Genetic Disorder Research
In treating conditions like spinal muscular atrophy (SMA), PEG-conjugated ASOs provide the extended half-life necessary for infrequent dosing, significantly improving patient compliance.
Infectious Diseases
Our delivery service supports the development of antiviral oligonucleotides that inhibit viral replication. PEGylation protects these agents from the harsh extracellular environment.
Cardiovascular Disease Research
PEGylated siRNAs offer a stable platform for modulating lipid metabolism or glucose levels, providing a long-acting therapeutic effect that reduces the burden of frequent administration.
Unrivaled Purity and Homogeneity
We utilize advanced purification protocols to ensure that our PEG-oligonucleotide conjugates are free from truncated sequences or unreacted polymers, resulting in a consistent and high-quality product for your critical research.
Customizable Polymer Architectures
CD BioGlyco offers a vast array of PEG structures, including linear, Y-shaped, and multi-arm configurations, allowing us to fine-tune the delivery profile for your specific oligonucleotide modality.
Enhanced PK Profiles
Our PEGylation technology is proven to increase the circulation half-life of oligonucleotides by several orders of magnitude, effectively reducing renal clearance and allowing for lower, more effective therapeutic dosages.
Reduced Immunogenicity and Toxicity
By shielding the negative charge and hydrophobic patches of oligonucleotides, our PEGylation service minimizes the risk of toll-like receptor (TLR) activation and unwanted immune responses in vivo.
"The team at CD BioGlyco provided exceptional support for our siRNA PEGylation project. The level of characterization, especially the MS data, was far superior to what we had received elsewhere."
– A.R., Research Institute
"We were struggling with the rapid clearance of our lead aptamer candidate. CD BioGlyco's branched PEG conjugation strategy extended the half-life, allowing us to move forward into our next phase of development."
– D.T., Biopharmaceutical Company
"Their ability to integrate pH-sensitive linkers into our PEG-ASO conjugates was a game-changer for our endosomal escape studies. The purity was excellent, and the technical support was highly responsive throughout the process."
– C.T., Innovative Therapeutics Firm
CD BioGlyco offers a premier, high-fidelity PEG-therapeutic oligonucleotide delivery service. By combining advanced polymer chemistry with rigorous analytical validation, we empower researchers to overcome the PK barriers of nucleic acid medicine. Please feel free to contact us to provide a customized solution for your delivery needs.
