GalNAc-Conjugated ASO
Development Service
Accelerating your RNA therapeutics with our gold-standard GalNAc conjugation platform. We provide end-to-end solutions from sequence design to preclinical validation, ensuring high liver specificity and enhanced metabolic stability.
Unlocking Liver-Targeted Delivery
GalNAc-conjugated Antisense Oligonucleotides (ASOs) represent a pivotal advancement in gene therapy. By conjugating N-acetylgalactosamine (GalNAc) ligands to the ASO, we leverage the high-affinity interaction with the Asialoglycoprotein Receptor (ASGPR), which is abundantly and exclusively expressed on the surface of hepatocytes.
This receptor-mediated endocytosis mechanism allows for rapid internalization of the therapeutic payload, resulting in significantly enhanced potency and reduced off-target toxicity compared to unconjugated ASOs.
Mechanism of Action: GalNAc-ASGPR Interaction
Our Services
Comprehensive support for your GalNAc-ASO development, from initial design to manufacturing.
GalNAc-Conjugated ASO Design
Custom design of ASO sequences targeting your specific RNA of interest. We optimize for hybridization affinity and select appropriate GalNAc linker configurations.
Chemical Synthesis & Modification
Advanced solid-phase synthesis incorporating chemical modifications (2'-MOE, cEt, PS backbone) to enhance nuclease resistance, combined with precise GalNAc conjugation.
Preclinical Data Analysis & Optimization
PAnalyze preclinical data to improve ASO design and enhance its potential in various applications.
Animal Model Testing
Initial in vivo efficacy validation using rodent models. Services include biodistribution tracking, liver accumulation studies, and target knockdown confirmation.
Preclinical Research
GLP-like toxicology, pharmacokinetics (PK), and pharmacodynamics (PD) profiling to provide robust data packages for your ASO drug candidates.
In Vitro Validation
Functional validation using primary hepatocytes and cell lines. We assess binding affinity (Kd), cellular uptake, and gene knockdown efficiency (mRNA/Protein levels).
Applications of GalNAc-Conjugated ASO
GalNAc-ASO technology has revolutionized the treatment of liver-associated diseases. By efficiently silencing disease-causing genes in hepatocytes, we unlock new therapeutic possibilities for conditions previously considered undruggable.
Cardiovascular & Metabolic Diseases
Targeting genes involved in lipid metabolism (e.g., PCSK9, APOC3, ANGPTL3) to treat hypercholesterolemia and hypertriglyceridemia.
Rare Genetic Disorders
Therapies for conditions like Hereditary Transthyretin Amyloidosis (hATTR) and Acute Hepatic Porphyria (AHP) by reducing the production of toxic proteins.
Infectious Diseases
Development of functional cures for Hepatitis B Virus (HBV) infection by silencing viral transcripts and reducing HBsAg burden.
Liver Fibrosis & NASH
Targeting key regulators of inflammation and fibrosis in hepatocytes to halt or reverse the progression of Non-Alcoholic Steatohepatitis (NASH).
Technical Advantages
High Specificity
GalNAc conjugation ensures precise targeting of hepatocytes via ASGPR, significantly minimizing uptake in non-target tissues like the kidney and reducing systemic toxicity.
Optimized Stability
Through a combination of phosphorothioate backbones and 2' modifications (e.g., 2'-MOE), we ensure long-term in vivo stability, enabling less frequent dosing regimens.
Application Potential
Our mature platform holds promise for developing new approaches to research methods for various liver-related genetic diseases, metabolic disorders, and viral infections.
Development Process
A streamlined workflow designed to accelerate your drug discovery timeline.
Analysis
Requirements analysis & preliminary design.
Synthesis
Chemical synthesis & molecular modification.
In Vitro
Functional validation & stability screening.
Animal Testing
Rodent efficacy models & biodistribution.
Preclinical
Preparation & support for clinical research.
Case Studies & Results
Metabolic Disease Target
Client: Biotech Startup
Result: We developed a GalNAc-ASO candidate that achieved >90% knockdown of the target mRNA in mouse liver at a dose of 2.5 mg/kg, with sustained effects observed for over 4 weeks.
"The specificity and potency of the conjugate exceeded our expectations and accelerated our IND filing."
Viral Hepatitis Research
Client: Pharmaceutical Co.
Result: Successfully synthesized a multi-valent GalNAc-ASO that demonstrated a 10-fold increase in hepatocyte uptake compared to the naked ASO in vitro.
"Professional execution from synthesis to validation. The stability data was particularly impressive."
Frequently Asked Questions
GalNAc (N-acetylgalactosamine) binds with high affinity to the Asialoglycoprotein Receptor (ASGPR), which is exclusively and abundantly expressed on hepatocytes. This enables targeted delivery of ASOs to the liver, allowing for lower doses and reduced systemic side effects compared to non-conjugated ASOs.
We support a wide range of state-of-the-art modifications to enhance stability and potency, including 2'-MOE, 2'-OMe, cEt (constrained ethyl), LNA (Locked Nucleic Acid), and Phosphorothioate (PS) backbones.
GalNAc-conjugated ASOs are primarily used for genetic liver diseases such as familial hypercholesterolemia, genetic mutations causing rare metabolic disorders, and some viral infections, such as hepatitis. They can also be useful in targeting specific disease-related RNA in the liver.
The development timeline can vary depending on the specific project and its complexity. On average, it takes several months for the design and synthesis of the ASO, followed by in vitro testing. In vivo testing and preclinical validation may take additional months. However, each stage is critical to ensuring the safety and efficacy of the final product.
The design process involves identifying the target RNA sequence that is responsible for the disease and then creating an ASO sequence that binds specifically to this RNA. The GalNAc moiety is conjugated to the ASO to enhance liver-specific delivery. We ensure the ASO’s stability, potency, and safety through rigorous testing.
The primary advantage of using GalNAc-conjugated ASOs is their ability to target the liver with high specificity. This targeted delivery reduces off-target effects and enhances therapeutic efficacy in treating liver diseases. Additionally, GalNAc conjugation improves the ASO’s stability and bioavailability, allowing for more effective treatments.
Tell us about your project, and our experts will get back to you with a customized quote and proposal.
