Advanced Delivery Platform

Antibody-Conjugated
ASO Development

Bridging the gap between genomic precision and targeted delivery. We engineer chimeric molecules that overcome biological barriers.

Explore Technology

Redefining RNA Therapeutics

Antibody-Oligonucleotide Conjugates (AOCs) are the next frontier in precision medicine. While Antisense Oligonucleotides (ASOs) offer potent gene silencing, they struggle with cellular uptake and tissue specificity.

"By harnessing the targeting power of monoclonal antibodies, we hijack natural receptor-mediated pathways to deliver therapeutic payloads exactly where they are needed."

Our integrated platform solves the critical "drug delivery problem," enabling researchers to make breakthroughs in diseases affecting muscle, heart, and central nervous system tissues that were previously inaccessible..

98% Purity Target
10+ Linker Types
500+ Projects Delivered
AOC Concept

Conjugation Technology

Precise chemical engineering strategies designed to maintain stability and maximize activity.

Chemical Methods

We employ site-specific conjugation technologies such as Cysteine re-bridging, Enzymatic labeling, and Click chemistry to control the Drug-to-Antibody Ratio (DAR) precisely and maintain antibody affinity.

Linker Design

Our library includes both cleavable (Val-Cit, disulfide) and non-cleavable linkers. We match the linker strategy to the target tissue's intracellular environment (pH, enzymes) to ensure optimal payload release.

Stability & Efficiency

Rigorous formulation development ensures the conjugate remains stable in plasma without aggregation, maximizing delivery efficiency to the target organ and minimizing renal clearance.

Conjugation Technology Illustration

Research Focus Areas

We provide specialized AOC development solutions for therapeutics targeting diseases that are challenging to treat with conventional modalities.

Oncology

Solid tumors, Metastasis & Tumor Microenvironment.

Neurodegenerative

Alzheimer's, ALS & Crossing the Blood-Brain Barrier.

Muscular Dystrophy

DMD, Myotonic Dystrophy & Muscle targeting.

Rare Diseases

Orphan indications, Metabolic disorders & Enzyme defects.

Antibody Optimization

The vehicle determines the destination. We select antibodies not just for binding, but for their ability to carry the payload into the cell.

"Optimal internalization kinetics are as critical as binding affinity."

Strict Screening Parameters

  • Affinity Nanomolar binding to target antigen (Kd < 10nM).
  • Specificity Validated against a panel of 50+ normal tissue types.
  • Internalization >50% internalization within 2 hours of binding.

Antibody Engineering

We modify candidates to enhance their therapeutic index:

Humanization

Grafting CDRs onto human frameworks to reduce immunogenicity.

Fc Silencing

Mutations (e.g., LALA-PG) to prevent ADCC/CDC effector functions.

Cys-Engineering

Introducing site-specific cysteines (ThioMab) for precise conjugation.

Half-life Extension

FcRn affinity optimization for longer circulation.

Rigorous Validation

Flow Cytometry
Binding
Confocal Microscopy
Trafficking
SPR (Biacore)
Kinetics
In vivo Imaging
Biodistribution

The AOC Advantage

Comparing the performance profile of Antibody-Conjugates vs. Naked ASOs.

Parameter Naked ASO Antibody-Conjugated ASO
Tissue Specificity Low (Accumulates in Liver/Kidney) High (Antigen-Driven)
Cellular Uptake Inefficient (Relies on Gymnosis) Active (Receptor-Mediated Endocytosis)
Therapeutic Index Narrow Broad (Lower Dose Required)
Systemic Half-Life Short (Rapid Clearance) Extended (Fc-Mediated Recycling)

Our Distinctive Features

Rich Project Experience

Dual-Expertise Platform

Most CROs specialize in either Biologics or Chemistry—rarely both. Creative Biolabs possesses deep in-house expertise in both Antibody Engineering and Oligonucleotide Chemistry. This allows us to optimize the entire molecule as a single functional unit, preventing the common "siloed" development issues.

In-house Linker Synthesis Process Development PhD Expertise

Development Workflow

1

Consultation

Target definition, sequence selection & feasibility assessment.

2

Engineering

Antibody modification (Cys/Lys) & Oligo functionalization.

3

Conjugation

Precise chemical linking, purification & DAR analysis.

4

Validation

In vitro potency assays, uptake studies & stability testing.

Success Stories

Muscular Dystrophy

Targeting Skeletal Muscle

Challenge: Naked ASO showed poor efficacy in DMD models due to lack of uptake.
Solution: Conjugated to anti-TfR1 antibody.

Result:

15-fold increase in muscle conc.
CNS Delivery

Crossing the Blood-Brain Barrier

Challenge: Achieving systemic delivery to the brain without invasive injection techniques.
Solution: Developed a BBB-shuttle bispecific antibody-ASO.

Result:

50% mRNA knockdown in cortex

Why Partner with Creative Biolabs?

End-to-End Support

From antibody discovery to IND-enabling studies, we handle every step of the pipeline.

Proprietary Tech

Access to exclusive linkers and conjugation methods that ensure high yield and purity.

Flexibility

Modular project scopes to fit your budget, timeline, and specific scientific needs.

Frequently Asked Questions

An Antibody-Conjugated ASO (often referred to as an Antibody-Oligonucleotide Conjugate or AOC) is a chimeric therapeutic molecule. It chemically links a therapeutic Antisense Oligonucleotide—which is designed to silence or modify the expression of a disease-causing gene—to a Monoclonal Antibody (mAb). The antibody serves as a delivery vehicle, leveraging its high affinity for specific cell-surface receptors to transport the ASO payload directly into the target tissue, thereby overcoming the delivery challenges associated with naked oligonucleotides.
The mechanism involves several key steps:
  1. Binding: The antibody component binds specifically to a receptor on the surface of the target cell (e.g., Transferrin receptor for muscle/CNS targeting).
  2. Internalization: This binding triggers receptor-mediated endocytosis, pulling the conjugate into the cell.
  3. Release: Once inside the endosome, the linker connecting the antibody and ASO is cleaved (or the ASO escapes via other mechanisms), releasing the payload.
  4. Action: The free ASO traffics to the nucleus or cytoplasm, where it binds to its target mRNA to inhibit translation or modulate splicing, treating the disease at the genetic level.
Conjugating ASOs to antibodies offers transformative benefits over "naked" ASO administration:
  • Tissue Specificity: It directs the drug to specific organs (e.g., heart, muscle) rather than accumulating in the liver and kidneys.
  • Enhanced Potency: Active transport allows for higher intracellular concentrations of the drug.
  • Lower Toxicity: Because less drug is required to achieve a therapeutic effect, systemic side effects are minimized.
  • Bioavailability: Antibodies can facilitate crossing biological barriers, such as the Blood-Brain Barrier (BBB), which are typically impermeable to naked ASOs.
Our selection process is rigorous and multi-faceted. We screen antibody libraries not just for high binding affinity, but specifically for internalization efficiency—ensuring the antibody is rapidly taken up by the cell after binding. Once a candidate is selected, we perform engineering to optimize it for conjugation:
  • Humanization: Reducing immunogenicity for clinical safety.
  • Fc Silencing: Mutating the Fc region to prevent unwanted immune system activation (ADCC/CDC).
  • Site-Specific Engineering: Introducing specific attachment points (like engineered Cysteines) to ensure a consistent Drug-to-Antibody Ratio (DAR) and product homogeneity.
The timeline varies based on the scope of the project. A standard custom conjugation project (using a client-supplied antibody and ASO) typically takes 4-8 weeks, including purification and QC. However, a comprehensive end-to-end development program—encompassing antibody discovery, linker optimization, in vitro screening, and in vivo efficacy studies—is more complex. We provide a detailed Gantt chart and milestone plan with every custom proposal to ensure transparency and alignment with your research goals.

Start Your Project Today

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