Tri-antennary GalNAc conjugates for liver-targeted oligos
N-acetylgalactosamine (GalNAc) ligands conjugated to siRNA, ASO or antisense payloads route uptake via asialoglycoprotein receptor (ASGPR) on hepatocytes. Tri-antennary GalNAc clusters are the dominant motif for systemic subcutaneous dosing in modern RNAi programs.
Tri
antennary GalNAc
ASGPR
hepatocyte uptake
SC
common route (indicative)
siRNA / ASO
payload types
1–3
GalNAc units per conjugate (typical)
Tri-antennary GalNAc design
A tri-antennary cluster presents three GalNAc residues on a scaffold (often lysine or proprietary linker) attached to the 3' or 5' terminus of the oligo or to a selective linkage on the sense strand of a siRNA.
Conjugate integrity is verified by mass spectrometry: both oligo and carbohydrate contribute distinct mass signatures. Aggregation and hydrophobic interaction chromatography help separate unconjugated starting material.
Conjugation attachment points
| Payload | Common linkage site | Consideration |
|---|---|---|
| siRNA duplex | Sense strand 3' or terminal | Preserve guide strand for RISC loading |
| ASO | 3' terminus | Minimize interference with RNase H gap if 3' proximal |
| multi-GalNAc | Scaffold acetylation complete | Deprotected GalNAc for ASGPR binding |
| Control | Scrambled GalNAc or glucose | Uptake specificity in hepatocyte assays |
Figures are indicative industry-typical values. Lot- and project-specific data appear on the quotation and certificate of analysis.
Indicative GalNAc conjugate specs
Identity
HRMS
Oligo + linker + GalNAc mass
Conjugation efficiency
Reported %
Residual naked oligo tracked
Duplex integrity
For siRNA-GalNAc
Tm and duplex purity post-conjugation
Purity
HIC / RP-HPLC
Hydrophobic conjugates
Endotoxin
When in vivo tier ordered
Per specification
Figures are indicative industry-typical values. Lot- and project-specific data appear on the quotation and certificate of analysis.
GalNAc and linker options
GalNAc motifs
- Tri-antennary GalNAc on lysine scaffold
- Mono- and di-GalNAc for dose-finding
- GalNAc variants (acetylation state per synthesis route)
Linkers
- PEG spacers (variable length)
- Non-cleavable amide / thioether
- Cleavable linkers (project-specific, if qualified)
Payload pairings
- GalNAc-siRNA duplex
- GalNAc-ASO (single strand)
- Multi-conjugate exploratory formats
What you receive
- GalNAc conjugate with full MS identity
- Reported conjugation ratio and residual unconjugated oligo
- For siRNA: duplex QC including guide/passenger traceability
- Handling notes for aqueous solubility of hydrophobic conjugates
- Stability hold data on request for formulation planning
- Quote referencing GalNAc valency and scale
Frequently asked questions
Tri-antennary clusters are the industry default for potent hepatocyte uptake. Mono-GalNAc can be used for SAR or control arms.
Related
siRNA Duplexes
Chemically modified siRNA duplexes for RNAi: antisense (guide) and sense (passenger) strands annealed under controlled conditions. Strand-specific identity, duplex integrity and residual single strands are documented for screening through IND-enabling supply.
View detailsAntisense (ASO)
Single-stranded phosphorothioate-rich ASOs for RNase H–mediated knockdown (gapmers) or sequence-specific binding without degradation (steric blockers). Chemistry, length and modification pattern are chosen to the target transcript, tissue and intended clinical dose.
View detailsPeptide & Lipid Conjugates
Oligos linked to cell-penetrating peptides (CPP), peptide-PMO (PPMO) constructs, cholesterol and other lipid anchors, and miscellaneous delivery ligands. Conjugation chemistry preserves oligo integrity while enabling uptake in muscle, CNS and other tissues beyond GalNAc-liver programs.
View detailsClinical & Commercial GMP
GMP manufacturing of oligonucleotide drug substance for clinical trials and commercial supply: batch records, validated release and stability methods, change control, and documentation packages suitable for regulatory filing — described at capability level without inventing facility certifications.
View detailsOligo NCE / CMC Development
Chemistry, manufacturing and controls for oligonucleotide new chemical entities: route scouting on solid-phase synthesizers, impurity fate studies, specification setting, stability protocols and regulatory-ready documentation — without implying a specific plant configuration.
View detailsReady to specify this for your program?
Share sequence, scale and documentation needs. We reply with indicative specs and a project-specific quotation.