Advanced Nucleic Acid Delivery

ASO Conjugate
Development Services

Overcoming the delivery barrier is critical for the success of nucleic acid therapeutics. Creative Biolabs provides comprehensive Antisense Oligonucleotide (ASO) conjugation services—from GalNAc to Antibodies—to enhance cellular uptake and enable tissue-specific targeting.

Our Conjugation Services

We offer a diverse portfolio of conjugation strategies tailored to your specific therapeutic targets and delivery requirements.

Our Technology Platform for ASO Conjugate Development

Leveraging proprietary technologies to accelerate the discovery and optimization of next-generation nucleic acid therapeutics.

Bio-Orthogonal Conjugation Hub

Our platform utilizes advanced "click" chemistry (e.g., SPAAC, CuAAC) and enzymatic conjugation methods to attach ligands to ASOs with high specificity and yield, ensuring no interference with the antisense activity.

Linkerology Optimization

We design smart linkers that balance circulation stability with efficient intracellular release. Our library includes redox-sensitive, pH-sensitive, and enzyme-cleavable linkers tailored for specific tissue microenvironments.

High-Resolution Analytics

Integrated with high-resolution LC-MS, NMR, and HPLC, our analytical platform ensures precise characterization of Drug-to-Antibody Ratio (DAR), conjugation sites, and purity (>95%) for IND-enabling studies.

Applications of ASO Conjugates

By modifying the physicochemical properties of ASOs through targeted conjugation, we enable a wide range of therapeutic and research applications that were previously inaccessible.

"By attaching a "targeting key" (ligand) to the ASO, developers can unlock specific cell types, lower the required dose, and reduce side effects."

High-Potency Hepatocyte Targeting

GalNAc conjugation utilizes the asialoglycoprotein receptor (ASGPR), which is abundantly and exclusively expressed on hepatocytes. This allows for the delivery of ASOs with exceptional potency and specificity, significantly reducing the required dose for metabolic disease treatments and minimizing renal accumulation.

Crossing Biological Barriers

Peptide conjugates (such as cell-penetrating peptides) and specific receptor ligands (such as transferrin receptor binders) are being developed to cross the blood-brain barrier (BBB) or enhance absorption in muscle tissue. This opens up new avenues for the development of drugs for muscular dystrophy and neurodegenerative diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis (ALS).

Extending Therapeutic Duration

Lipid and polyethylene glycol (PEG) conjugates alter the drug's interaction with plasma proteins such as albumin, reduce rapid renal clearance, and protect the antisense oligonucleotide (ASO) backbone from exonuclease degradation. This prolongs the drug's circulating half-life, thereby reducing dosing intervals.

Visualizing Drug Mechanisms

Fluorophore-conjugated ASOs allow researchers to visualize intracellular trafficking in real-time. This is essential for confirming endosomal escape efficiency, validating tissue distribution in preclinical animal models, and understanding the kinetics of cellular uptake.

Impact of Conjugation

Comparison of key properties across different conjugation strategies.

Conjugation Type Target Receptor Uptake Efficiency Primary Benefit
GalNAc ASGPR (Liver) Very High Liver specificity & high potency
Antibody (AOC) Specific Antigens (e.g., TfR1) High Extra-hepatic targeting (Muscle/CNS)
Lipid (Cholesterol) Lipoprotein Receptors Broad Systemic distribution & PK
Peptide (CPP) Cell Membrane / Endosome High Endosomal escape
Polymer (PEG) Passive Shielding Low Stealth & Reduced Clearance

Workflow of ASO Conjugation

Streamlined from design to delivery.

1

Design & Selection

Consultation to select optimal ligands (GalNAc, Antibody, Lipid) and linker chemistry (cleavable vs. non-cleavable) tailored to your target tissue.

2

Synthesis

Solid-phase synthesis of the ASO backbone (PS, 2'-OMe, MOE) incorporating precise functional groups (amino, thiol, alkyne) for conjugation.

3

Conjugation

Coupling of the ligand to the ASO using advanced chemistries (Click, Amide bond), followed by rigorous HPLC purification.

4

QC & Analysis

Comprehensive characterization via LC-MS (MW) and HPLC (purity) to ensure the final product meets preclinical standards (>90% purity).

Why Choose Creative Biolabs?

Icon

Extensive Ligand Library

Access pre-validated ligands including GalNAc clusters, lipophilic moieties, antibodies, and peptides.

Icon

Smart Linkers

Stable, acid-labile, and reduction-sensitive linkers to control payload release within the cell.

Icon

High Purity & Yield

Optimized protocols maximize yield while minimizing side reactions, ensuring >90% purity.

Icon

Analytical Excellence

Rigorous QC with high-resolution MS and HPLC confirms identity and purity.

Icon

Fully Customizable

Custom synthesis from sequence design to specific conjugation sites (5' end, 3' end, or internal).

Icon

One-Stop Solution

From ASO design and synthesis to conjugation, purification, and in vitro screening.

Customer Success Stories

Dr. Sarah Jenkins

Dr. Sarah Jenkins

Principal Investigator

"We were struggling with in vivo delivery to hepatocytes. Creative Biolabs synthesized a GalNAc-conjugated version of our sequence. The increase in potency was remarkable—gene knockdown at a fraction of the previous dose."

Mark Thompson

Mark Thompson

Senior Scientist

"The team helped us attach a fluorophore for tracking studies. The labeling efficiency was high and the signal stable. Their technical support regarding linker choice for endosomal escape was invaluable."

Frequently Asked Questions

Linker chemistry is critical for the stability and efficacy of the conjugate. We design linkers based on the specific application:

  • Cleavable Linkers: Engineered to release the free ASO payload within specific intracellular environments (e.g., acidic endosomes or reducing cytoplasm).
  • Non-cleavable Linkers: Designed for maximum stability in circulation; suitable when the ASO retains activity while attached to the ligand.

We carefully optimize linker hydrophobicity, length, and attachment sites to ensure the conjugation does not interfere with the ASO's hybridization to its target RNA.

Unmodified ASOs often suffer from rapid nuclease degradation and fast renal clearance. Conjugation significantly enhances these properties by:

  • Increasing Stability: Protecting the oligonucleotide backbone from nuclease attack.
  • Tissue Specificity: directing the drug to specific tissues (e.g., liver targeting via GalNAc), which minimizes off-target toxicity.
  • Potency: Improving cellular uptake allows for lower dosing regimens and a wider therapeutic window.

Due to the complexity of conjugation reactions, high purity is essential. Our rigorous QC process includes:

  • Purification: Utilizing Reversed-Phase HPLC (RP-HPLC) or Ion Exchange Chromatography (IEX) to remove unreacted ASOs, free ligands, and failure sequences.
  • Characterization: Confirming molecular weight and identity using High-Resolution LC-MS.
  • Purity Analysis: Ensuring the final product meets strict purity standards (typically >90% or >95%) and endotoxin limits suitable for pre-clinical studies.

We offer flexible synthesis scales to support various stages of drug development.

  • Discovery Scale (Microgram to Milligram): Ideal for high-throughput screening of multiple conjugate candidates to identify the best lead.
  • Pilot Scale (Gram to Multi-gram): Suitable for animal studies (PK/PD/Tox) and process development.
  • Customization: We can adapt our synthesis and conjugation protocols to accommodate specific chemical modifications or proprietary ligands provided by the client.
Start Your Project Today

Tell us about your project, and our experts will get back to you with a customized quote and proposal.

Start Your Project Today