Triantennary GalNac-RNA Delivery Service
Overview
Targeted delivery remains the cornerstone of effective nucleic acid therapeutics. At CD BioGlyco, our triantennary GalNAc-RNA delivery service provides a sophisticated solution for liver-specific gene silencing and therapeutic intervention. By utilizing the high affinity of triantennary GalNAc for the asialoglycoprotein receptor (ASGPR) on hepatocytes, we enable exceptionally precise delivery of RNA molecules, including siRNA and antisense oligonucleotides (ASOs), directly to their site of action. This approach bypasses the need for complex lipid nanoparticle (LNP) formulations for liver targeting, simplifying the drug development process and enhancing safety profiles. Our service is designed to support researchers from initial sequence design through to the production of high-purity, in vivo-ready conjugates.
Core Technologies
- ASGPR-Targeted Ligand Systems
We utilize trivalent GalNAc clusters that mimic natural glycoproteins, binding to ASGPR with nanomolar affinity to trigger rapid receptor-mediated endocytosis.
- Precision Linker Chemistry
Our proprietary linker technologies include advanced diamine-scaffolds and piperidine-based 1,3-diol structures, which provide superior stability and prevent chiral center formation during synthesis.
- Phosphorothioate (PS) Backbone Integration
We optimize the linkage between the ligand and the RNA oligomer using PS-linkages where necessary to enhance metabolic stability and silencing potency.
- Advanced Sugar Protection
Utilizing trimethoxytrityl (TMT) groups and optimized deprotection protocols, we ensure the integrity of the GalNAc sugar moieties throughout the automated solid-phase synthesis process.
- Pot-Economy Synthesis
Our streamlined synthetic routes reduce production time and costs while maintaining the high yields required for therapeutic development.
Unlocking Ultra-Potency: Triantennary GalNAc-RNA Delivery
- Custom GalNAc-siRNA Synthesis: Full synthesis of double-stranded RNA molecules (up to 30 nt) with integrated triantennary ligands.
- GalNAc-ASO Conjugation: Targeted antisense oligonucleotides for splice modulation or RNase H-mediated degradation.
- Multivalent Scaffold Options: Availability of various branching clusters, including trivalent and tetravalent GalNAc configurations.
- Scale-up Production: Synthesis from milligram to multi-gram scales to support everything from pilot studies to pre-clinical trials.
- Endotoxin-Free Processing: Specialized handling and filtration for in vivo-ready preparations.
Workflow
Sequence Design and Optimization
Our bioinformatics team analyzes your target mRNA to design siRNA or ASO sequences with high specificity and minimal off-target potential.
Ligand and Linker Customization
Based on your delivery requirements, we select or synthesize the most appropriate triantennary GalNAc scaffold and linker system.
Solid-Phase Automated Synthesis
RNA strands are synthesized using state-of-the-art phosphoramidite chemistry, integrating GalNAc moieties at the 3' or 5' terminus as required.
Duplex Annealing and Modification
For siRNA projects, sense and antisense strands are precisely annealed under RNase-free conditions to form stable duplexes.
Rigorous Purification
We employ multiple HPLC stages and counter-ion exchange to achieve >97% purity, ensuring the conjugates are ready for sensitive in vivo applications.
Comprehensive Quality Control
Every batch undergoes mass spectrometry and analytical HPLC to verify molecular weight, sequence accuracy, and purity levels.
Publication Data
Journal: Molecules
DOI: 10.3390/molecules29245959
Published: 2024
IF: 4.6
Results: In this study, the authors introduce a novel pot-economy synthesis method for triantennary GalNAc conjugates, which are essential for targeted delivery of oligonucleotide therapeutics to hepatocytes via asialoglycoprotein receptor-mediated endocytosis. Traditional synthesis routes often involve multiple purification steps, high solvent consumption, and toxic reagents like palladium. The new approach strategically divides the process into two pots, utilizing greener alternatives such as AlCl3 and FeCl3 to avoid rare metals, thereby aligning with green chemistry principles by enhancing atom economy and reducing hazardous waste. This optimized method achieves a remarkable yield of up to 61%, with significant reductions in reagent and solvent use compared to prior techniques. Furthermore, the authors successfully extend the synthesis to produce GalNAc phosphoramidite and CPG derivatives, facilitating efficient incorporation into oligonucleotides for therapeutic applications. This work provides a scalable, cost-effective, and environmentally friendly pathway for advancing RNAi-based drugs.
Applications
Metabolic Disease Research
Targeting genes involved in lipid metabolism, glucose regulation, and cholesterol synthesis to develop treatments for NAFLD, NASH, and familial hypercholesterolemia.
Cardiovascular Therapeutics
Silencing hepatic targets like PCSK9 or Angptl3 to manage cardiovascular risk factors through highly specific, liver-directed RNA interference.
Chronic Viral Infections
Developing GalNAc-siRNA conjugates that target conserved viral RNA sequences in hepatocytes, providing a potent tool for research into Hepatitis B and Hepatitis C.
Rare Genetic Disorders
Addressing orphan diseases caused by hepatic protein deficiencies or toxic gain-of-function mutations through precise modulation of liver-specific gene expression.
Advantages
Unmatched Hepatocyte Selectivity
Our triantennary GalNAc clusters demonstrate exceptional specificity for hepatic tissue, significantly reducing systemic toxicity and minimizing exposure to non-target organs and tissues.
Superior Nuclease Resistance
Through the integration of advanced 2' modifications and PS linkages, our RNA conjugates resist degradation in the bloodstream, ensuring a higher percentage of the dose reaches the target receptors.
High-Purity Manufacturing
We utilize state-of-the-art purification technologies to provide conjugates with industry-leading purity levels, ensuring that experimental results are not confounded by synthesis byproducts or residual ligands.
Customizable Linker Chemistry
Clients can choose from a variety of linker lengths and chemical compositions to optimize the spatial orientation of the ligand, which is critical for achieving the highest possible receptor affinity.
Frequently Asked Questions
Customer Review
The hepatocyte targeting efficiency of the GalNAc-siRNA conjugates provided by CD BioGlyco exceeded our expectations. The silencing effect in our murine models was both potent and durable.
— Dr. A. Thompson, Principal Investigator, Department of Molecular Medicine
We have switched all our liver-directed ASO projects to CD BioGlyco. Their triantennary scaffold is highly consistent, and the purity levels are exactly what we need for our preclinical validation studies.
— Manager, Pharmacology Division, Therapeutic Development Unit.
The technical support at CD BioGlyco is outstanding. They helped us optimize the chemical modification pattern of our RNA, which significantly improved the in vivo half-life of our conjugates.
— Dr. L. Chen, Senior Scientist, Liver Research Laboratory
Fast turnaround and impeccable quality. The triantennary GalNAc delivery platform has accelerated our lead optimization phase by several months. Highly recommended for any RNA therapeutics group.
— Director of Research, Nucleic Acid Chemistry Department
Associated Services
CD BioGlyco is a leader in the field of targeted RNA delivery. Our triantennary GalNAc-RNA delivery service provides the precision, stability, and potency required to move hepatic research forward. By combining cutting-edge multivalent ligand technology with rigorous quality control, we empower our clients to achieve superior therapeutic outcomes. For detailed project discussions, technical inquiries, or to request a formal quotation, please contact us.
Reference
- Gusev, A.E.; et al. A novel pot-economy approach to the synthesis of triantennary GalNAc-oligonucleotide. Molecules. 2024, 29(24): 5959. (Open Access)