GalNAc Conjugate
Precision-Controlled GalNAc ConjugationDevelopment-Ready GalNAc ConjugatesASGPR-Targeted Liver Delivery Technologies
Accelerate liver-targeted drug development with high-performance GalNAc conjugation services purpose-built for enterprise R&D teams in biotechnology, pharmaceutical development, and CDMO environments. Our GalNAc conjugation platform is grounded in scalable chemistry, well-controlled reaction design, and rigorous analytical characterization—enabling the production of GalNAc-conjugated biomolecules with consistent quality, defined conjugation profiles, and development-relevant reproducibility. We support GalNAc conjugation of siRNA, ASO and therapeutic oligonucleotides, peptides, and selected small-molecule payloads, as well as custom ligand–linker architectures designed for ASGPR-mediated hepatocyte uptake.
Whether your program focuses on RNA therapeutics, liver-selective delivery, systemic exposure reduction, or preparation for preclinical and IND-enabling studies, our GalNAc conjugates are developed with practical manufacturing considerations in mind. We emphasize controlled ligand attachment, impurity reduction, and batch-to-batch consistency to support reliable in vitro and in vivo performance, comparability studies, and downstream scale-up planning across development stages.
What Is GalNAc Conjugation?
GalNAc (N-acetylgalactosamine) conjugation enables targeted delivery to hepatocytes by exploiting the asialoglycoprotein receptor (ASGPR), a highly expressed receptor on liver cells. By covalently attaching multivalent GalNAc ligands to siRNA, antisense oligonucleotides (ASOs), peptides, or other biomolecules, GalNAc conjugates drive efficient receptor-mediated uptake, improving liver exposure while reducing off-target distribution. Our service specializes in controlled GalNAc attachment with rigorous characterization to preserve payload integrity, optimize ligand density, and ensure manufacturable, scalable constructs suitable for discovery, preclinical, and clinical-stage programs.
GalNAc–siRNA conjugation enables precise, ASGPR-mediated delivery to hepatocytes, supporting next-generation liver-targeted RNA therapeutics.What Problems We Solve
Insufficient Liver Uptake
We optimize GalNAc valency, linker architecture, and attachment sites to maximize ASGPR affinity and hepatocyte uptake for liver-targeted delivery.
Payload Integrity Loss
Mild, application-matched conjugation conditions preserve oligonucleotide integrity, peptide structure, and functional activity throughout the process.
Impurity & Byproduct Burden
Advanced purification workflows remove unconjugated ligand, partially substituted species, and process impurities to enable clean, interpretable data.
Uncontrolled Ligand Density
We control degree of substitution (DoS) and distribution using chemistry selection plus analytical feedback (LC-MS, HPLC/UPLC), ensuring reproducibility.
Scale-Up & Manufacturability Risks
Robust process design and scalable purification reduce aggregation, improve yield, and support tech transfer from mg to multi-gram programs.
Complex Substrate Challenges
We successfully conjugate difficult constructs—including heavily modified oligos, hydrophobic payloads, and sterically constrained sites—where standard methods fail.
Our GalNAc Conjugation Services
To support the diverse needs of liver-targeted delivery programs, we provide GalNAc conjugation services tailored to specific molecular modalities. Each modality presents distinct challenges in terms of conjugation chemistry, heterogeneity control, analytical characterization, and scalability. Our molecule-type–driven services are designed to align GalNAc attachment strategies with the physicochemical and biological properties of each payload, enabling efficient ASGPR-mediated hepatocyte uptake while preserving payload integrity and development readiness.
GalNAc Conjugation of siRNA
We design and execute GalNAc conjugation strategies for siRNA constructs to enable efficient liver targeting via ASGPR-mediated uptake. Our workflows emphasize site control, controlled ligand density, and compatibility with chemically modified siRNA commonly used in therapeutic development.
- Triantennary GalNAc (3x GalNAc) attachment strategies optimized for hepatocyte uptake
- Site-specific conjugation at defined 3'/5' or internal positions to minimize heterogeneity
- Compatibility with standard siRNA chemistries (2'-OMe, 2'-F, phosphorothioate modifications)
- Purification workflows to remove unconjugated ligand and partially substituted species
- Analytical confirmation of identity, purity, and conjugation profile to support PK/PD studies
GalNAc Conjugation of ASO & Therapeutic Oligonucleotides
Our GalNAc conjugation services for ASO and other therapeutic oligonucleotides focus on balancing liver uptake, chemical stability, and manufacturability. We support both early discovery and translational programs requiring reproducible conjugation profiles.
- GalNAc attachment to ASO, splice-switching oligos, and custom oligonucleotide formats
- Handle-based and synthesis-integrated conjugation strategies for site control
- Linker and spacer selection to optimize exposure and intracellular processing
- High-resolution analytical characterization (LC-MS, HPLC/UPLC)
- Process designs compatible with scale-up and partner transfer
GalNAc Conjugation of Peptides & Peptide Ligands
We provide GalNAc conjugation for peptides and peptide ligands used in liver-targeted delivery research and mechanistic studies. Conjugation strategies are selected to preserve peptide structure and biological activity.
- N-terminal, C-terminal, or site-selective GalNAc attachment on linear and cyclic peptides
- Spacer engineering to reduce steric interference and maintain receptor engagement
- Purification via preparative HPLC with defined purity targets
- LC-MS-based identity and substitution verification
- Formulation guidance for aqueous compatibility and storage stability
GalNAc Conjugation of Proteins (Exploratory & Research Use)
For selected exploratory and research applications, we offer GalNAc conjugation of proteins to evaluate liver targeting concepts and receptor-mediated uptake. Strategies are chosen to control substitution levels and preserve protein function.
- Controlled GalNAc attachment via amine-, thiol-, or handle-directed chemistries
- Substitution level tuning to balance targeting and functional activity
- Purification by SEC or ultrafiltration to remove free ligand and aggregates
- QC including intact mass, purity, and aggregation assessment
In addition to molecule-specific conjugation, we offer specialized GalNAc-focused services that address key technical differentiators in today's liver-targeted delivery landscape. These service-driven capabilities support program optimization, scalability, and decision-quality data generation across multiple development stages.
GalNAc Linker Engineering (Cleavable & Non-Cleavable)
Linker architecture plays a critical role in GalNAc conjugate performance. We design and evaluate cleavable and non-cleavable linkers to align stability, intracellular processing hypotheses, and manufacturing feasibility.
- Selection and design of cleavable vs. non-cleavable linker strategies
- Spacer length and composition optimization (PEG, alkyl, hybrid linkers)
- Attachment site assessment to reduce heterogeneity and preserve payload integrity
- Analytical-driven evaluation of linker impact on conjugation profile and stability
Triantennary GalNAc Ligand Synthesis & Custom Derivatives
We synthesize high-quality triantennary GalNAc ligands and custom derivatives designed for reproducible conjugation and scalable supply. Ligands are delivered in conjugation-ready formats to streamline downstream workflows.
- Triantennary GalNAc (3x GalNAc) scaffold synthesis with controlled quality
- Installation of conjugation handles (amine, thiol, azide/alkyne, activated esters)
- Custom spacer variants for structure–function exploration
- Chromatographic purification and structural confirmation
GalNAc Conjugate Analytics & Release-Ready Data Packages
Our analytical services focus on delivering clear, decision-quality data to support internal reviews, partner communication, and IND-enabling activities. Methods are selected based on payload class and program stage.
- Identity confirmation and conjugation profile analysis by LC-MS
- Purity and heterogeneity assessment by HPLC/UPLC and orthogonal methods
- Variant distribution and residual unconjugated ligand evaluation
- Reporting formats aligned with enterprise governance and partner expectations
Feasibility, Optimization & Scale-Up Support for Enterprise Programs
We support GalNAc conjugation programs beyond synthesis by providing feasibility assessment, optimization, and scale-up planning aligned with real-world development constraints.
- Early feasibility evaluation of conjugation chemistry and attachment sites
- Optimization of reaction conditions and purification strategies
- Control of conjugation heterogeneity and yield improvement
- Scale-up planning and tech transfer–ready documentation
Our GalNAc Conjugation Chemistry & Methods
Selecting the right GalNAc conjugation route depends on payload class (siRNA/ASO/oligos, peptides, proteins), required site control, desired heterogeneity profile, and downstream manufacturability. Below is a practical, market-aligned overview of the most commonly used and broadly supported GalNAc conjugation strategies in liver-targeted development programs.
| Conjugation Approach | Reactive Handle / Chemistry | Best-Fit Payloads | Typical Program Use | Key Considerations |
| Handle-Based Click Conjugation (SPAAC) | Azide + strained alkyne (DBCO/BCN) coupling (copper-free) | siRNA, ASO/oligonucleotides, peptides; select proteins with engineered handles | Site-specific GalNAc attachment; heterogeneity reduction in discovery-to-development | High selectivity and clean profiles; requires compatible handle installation on payload |
| Amide Coupling (Activated Ester) | NHS-activated GalNAc derivatives reacting with primary amines | Peptides, proteins, amine-handle oligos | Rapid feasibility builds; scalable chemistry for certain payloads | May produce broader substitution distributions on proteins unless site-controlled |
| Thiol-Selective Conjugation | Thiol-reactive groups (e.g., maleimide variants) with cysteine/thiol handles | Peptides/proteins with defined cysteines; specialty constructs | Site-directed protein/peptide GalNAc attachment | Strong site control with engineered cysteines; careful control of reduction/oxidation state |
| Oligonucleotide Synthesis-Integrated Attachment | GalNAc-bearing building blocks or protected intermediates incorporated during synthesis | Therapeutic oligonucleotides (ASO/siRNA strands, modified oligos) | High-control designs used in many market-standard GalNAc-oligo formats | Excellent site control; feasibility depends on sequence, modifications, and synthesis plan |
| Post-Synthetic End-Labeling (Handle-Directed) | Pre-installed terminal functional handle (amine/azide/thiol) + matching GalNAc derivative | siRNA, ASO/oligonucleotides | Fast iteration for screening panels and lead optimization | Flexible and commonly used; handle placement drives site specificity and product profile |
| Oxime / Hydrazone Ligation (Orthogonal) | Aldehyde/ketone handle + aminooxy/hydrazide-functional GalNAc | Specialty oligos/peptides; selected custom constructs | Orthogonal attachment when click/amide routes are suboptimal | Useful for controlled architectures; stability and conditions are project-dependent |
| Linker Architecture Selection (Cleavable vs. Non-Cleavable) | Program-driven linker choice integrated into any of the above approaches | siRNA/ASO/oligos, peptides; selected payloads | Uptake optimization, intracellular processing hypotheses, and development strategy alignment | Cleavability and spacer length can impact stability, exposure, and manufacturability |
| Process Optimization for Scale & Reproducibility | Reaction and purification optimization (conditions, stoichiometry, workup) | All payload classes | Batch-to-batch consistency for preclinical/IND-enabling supply and partner transfer | Focused on reducing partially conjugated species, improving yield, and enabling repeatability |
Quality Control & Data Delivered
Enterprise GalNAc programs typically require QC that is fit-for-purpose: confirm identity and conjugation profile, quantify purity and key variants, and provide documentation that supports comparability and program decisions. The table below reflects common, practical QC expectations across discovery, preclinical, and IND-enabling phases.
| Quality Attribute | Primary Method(s) | What It Confirms | Delivered Outputs |
| Identity / Mass Confirmation | LC-MS (payload-appropriate); intact mass where applicable | Expected molecular mass and presence of the GalNAc-conjugated product | Mass spectrum and interpretation summary / identity statement |
| Purity Profile | HPLC or UPLC (method selected by payload class) | Overall purity and separation of major variants/impurities | Chromatograms, % area reporting (as applicable), peak assignment notes |
| Conjugation Profile / Variant Distribution | LC-MS and/or chromatographic profiling (HPLC/UPLC) | Distribution of conjugated vs. partially conjugated species (project-dependent) | Variant/distribution summary and supporting analytical traces |
| Free Ligand / Residual Unconjugated Species | HPLC/UPLC method development and/or orthogonal checks (as needed) | Removal of unconjugated GalNAc ligand and small-molecule impurities (where relevant) | Evidence of cleanup (chromatograms) and narrative conclusions |
| Oligonucleotide Integrity (for siRNA/ASO/oligos) | LC-MS/HPLC/UPLC integrity review; duplex-related checks (project-dependent) | Integrity of the oligo strand(s) and absence of major degradation products | Integrity assessment summary and supporting traces |
| Aggregation / Size Variant (for proteins or complex constructs) | SEC (size-exclusion chromatography); optional SDS-PAGE | Presence of aggregates and major size variants | SEC trace, % monomer/aggregate (as applicable), gel image (if performed) |
| Concentration / Content | UV-Vis (where applicable), gravimetric or method-appropriate quantitation | Reported concentration/content for downstream formulation and dosing planning | Concentration report and calculation details (method-dependent) |
| Stability (Optional) | Storage stability and/or serum/plasma stability (project-dependent) | Conjugate stability under defined conditions relevant to program stage | Time-course summary, analytical snapshots, handling/storage recommendations |
| Documentation Package | Project report compilation | Traceability and consistency for enterprise reporting, partner review, and comparability | Batch record summary, methods overview, analytical package, CoA-style summary (if requested) |
General Workflow for GalNAc Conjugation Services
Project Assessment & Strategy Design
We evaluate payload type (siRNA/ASO/peptide/protein), target product profile, ASGPR targeting goals, and preferred GalNAc formats. A customized conjugation and analytics strategy is defined to align with enterprise timelines and decision points.
Sample Preparation & Pre-Processing
Incoming payloads are inspected and conditioned (buffer exchange/desalting if needed). We remove interfering components and confirm handle compatibility to support efficient, high-yield conjugation.
GalNAc Conjugation Reaction
Conjugation is performed using optimized conditions and controlled ligand-to-payload ratios. Site-specific and handle-directed strategies are used to reduce heterogeneity and improve comparability across batches.
Purification & Removal of Impurities
Unconjugated ligand, partially substituted species, and process impurities are removed using HPLC/UPLC, SEC, or ultrafiltration—tailored to payload class and enterprise quality requirements.
Quality Control & Data Verification
Each conjugate undergoes identity, purity, DoS/ratio verification, and integrity analysis. Optional stability testing and method development support IND-enabling packages and partner reporting.
Final Delivery & Technical Support
You receive the GalNAc conjugate with a comprehensive data package and handling guidance. Our technical team supports downstream planning, scale-up considerations, and vendor qualification discussions.
Advantages of Our GalNAc Conjugation Services
Proven ASGPR-Targeted Liver Delivery
Our GalNAc conjugation strategies are designed around well-established ASGPR biology, enabling efficient and selective hepatocyte uptake. By optimizing GalNAc valency, linker architecture, and attachment sites, we help enterprise teams achieve robust liver targeting while minimizing off-target exposure—a critical success factor in RNA therapeutics and liver-focused drug development.
Controlled Conjugation & Low Heterogeneity
We prioritize site-specific and handle-directed GalNAc attachment to control ligand density and reduce product heterogeneity. Through chemistry selection and purification optimization, we consistently limit partially conjugated species—improving batch-to-batch reproducibility and supporting reliable structure–activity relationship (SAR) and PK/PD interpretation.
Enterprise-Grade Analytics & Data Quality
Our GalNAc conjugation services are supported by high-resolution analytical characterization, including LC-MS, HPLC/UPLC, and orthogonal methods selected by payload class. Delivered data packages focus on identity, purity, and conjugation profile—providing decision-quality information suitable for internal governance, partner review, and IND-enabling workflows.
Scalable, Development-Oriented Processes
Our conjugation and purification workflows are designed with scalability and tech transfer in mind. From early discovery batches to multi-gram preclinical supply, we align chemistry choices, process robustness, and documentation with real-world development needs—helping enterprise teams reduce downstream manufacturing and CMC risk.
Applications of GalNAc Conjugate Technology
RNA Therapeutics for Liver Diseases
- Enable targeted delivery of siRNA and ASO therapeutics to hepatocytes via ASGPR-mediated uptake.
- Improve liver exposure while reducing systemic distribution and off-target effects.
- Support development programs in genetic, metabolic, infectious, and rare liver diseases.
- Widely adopted in both clinical-stage and commercial RNA therapeutics pipelines.
Lead Optimization & Structure–Activity Relationship (SAR) Studies
- Compare GalNAc valency, linker architecture, and attachment sites across candidate constructs.
- Generate reproducible conjugate panels to guide SAR-driven decision-making.
- Support data-driven optimization of uptake, stability, and PK/PD profiles.
- Accelerate selection of development-ready GalNAc conjugate formats.
Hepatocyte Uptake & Mechanism-of-Action Studies
- Investigate ASGPR-dependent cellular uptake using GalNAc-conjugated research tools.
- Study intracellular trafficking, endosomal processing, and payload release hypotheses.
- Benchmark GalNAc conjugates against alternative liver-targeting strategies.
- Support translational interpretation of in vitro and in vivo uptake data.
Preclinical & IND-Enabling Development
- Produce well-characterized GalNAc conjugates suitable for preclinical efficacy and safety studies.
- Generate analytical data supporting comparability, reproducibility, and scale-up feasibility.
- Reduce development risk through impurity control and stability assessment.
- Align conjugation workflows with regulatory and CMC expectations.
Assay Development & Screening Platforms
- Create GalNAc-conjugated reagents for ASGPR binding, uptake, and internalization assays.
- Support high-throughput screening with batch-consistent conjugates.
- Enable reliable readouts by minimizing unconjugated ligand and heterogeneous species.
- Facilitate internal platform validation and partner technology evaluation.
Platform Differentiation & Pipeline Expansion
- Explore custom GalNAc architectures, linker designs, and conjugation strategies to differentiate delivery platforms.
- Support multi-program liver-targeting strategies within enterprise pipelines.
- Enable IP generation through novel GalNAc conjugate designs and analytics.
- De-risk expansion into new liver-targeted modalities using validated conjugation workflows.
Custom GalNAc Conjugation Solutions for Liver-Targeted Programs
No matter what your liver-targeted delivery goals require—whether it's GalNAc-siRNA development, GalNAc-ASO optimization, or enterprise-scale analytical comparability—we provide customized GalNAc conjugation built for high-impact programs. Our experts guide you from ligand selection and linker design to conjugation strategy and QC deliverables, ensuring your work is reproducible, scalable, and decision-ready. Reach out to us for a quote or technical consultation, and let us help you build the right GalNAc conjugate strategy for your program.
Frequently Asked Questions (FAQ)
Which RNA modalities can be conjugated with GalNAc?
We support conjugation of:
siRNA (sense/antisense)
Antisense oligonucleotides (ASO)
Aptamers
Modified oligonucleotides (2'-F, 2'-OMe, 2'-MOE, PS backbone, etc.)
If you have a custom chemistry or a novel modality, we can assess feasibility.
What GalNAc architectures do you offer?
We provide multiple ligand formats depending on delivery needs:
Triantennary GalNAc (industry standard for high ASGPR affinity)
Monovalent GalNAc (screening or specific mechanisms)
Customized multi-valent designs
Cleavable or non-cleavable linker options
What information do you need to start a GalNAc conjugation project?
Typically:
RNA sequence and chemical modification patterns
GalNAc format preference (if applicable)
Target gene and intended application
Desired purity, scale, and analytical specifications
Whether in vitro / in vivo evaluation is required
We can also support sequence optimization upon request.
What analytical methods are included in the QC package?
Typical characterization includes:
LC-MS, UPLC, NMR
HPLC purity analysis
CE and duplex stability (Tm)
Endotoxin testing
Impurity mapping and identity confirmation
Custom analytical packages are available depending on program needs.
Do you support custom linkers or novel conjugation strategies?
Yes. We can evaluate and develop:
Cleavable linkers
PEG-based spacers
Novel ligand geometries
Proprietary GalNAc modifications
We welcome co-development and custom innovation projects.
