Antibody-Oligonucleotide Conjugates (AOC) Platform

Antibody-Oligonucleotide Conjugates (AOCs) Discovery Platform

Leverage the targeted delivery capabilities of antibodies to transport oligonucleotides directly to specific cells or tissues. Enhance therapeutic precision and reduce off-target effects in gene modulation, making AOCs a powerful tool for both research and drug development.

Discuss your AOC Project with a Scientist

Overview

Achieve targeted gene modulation with the precision and power of AOCs

Antibody-Oligonucleotide Conjugates (AOCs) are a next-generation therapeutic modality combining the targeting antibodies with the gene-silencing power of oligonucleotides (such as siRNA or ASO).

By leveraging precise molecular design, AOCs can selectively deliver siRNA, ASO, or other therapeutic oligonucleotides to disease-relevant tissues, addressing challenges like cell uptake and delivery efficiency.

Learn How AOCs Compare with Traditional Modalities

Our AOC Strategy

RNAi Platform:

Our RNAi discovery platform supports the synthesis and development of AOCs, leveraging advanced chemical modifications and delivery technologies. It is highlighted as:

Mononucleotide synthesis and modifications: Synthesis of over 80 unique monomers supporting diverse oligonucleotide designs

- Custom nucleobase analogs for diverse hybridization
- Backbone modifications for increased nuclease resistance
- Sugar modifications to fine-tune binding affinity, as well as abrogated off-target activity

Mononucleotide Synthesis
Medicilon Optimal Design (MOD)
GalNAc Synthesis and Optimization
Ionizable Lipid Synthesis

Mononucleotide Synthesis

Synthesis of over 80 unique monomers supporting diverse oligonucleotide designs

Custom nucleobase analogs for improved hybridization and nuclease resistance

Backbone modifications for increased half-life

Sugar modifications to fine-tune binding affinity

Medicilon Optimal Design (MOD)

Targeted sequence design leveraging the Medicilon Optimal Design (MOD) platform with focused-range prediction to enhance silencing efficacy

GalNAc Synthesis and Optimization

Broad-class GalNAc library creation (>2000 ionizable lipids synthesized)

Custom GalNAc linker designs for enhanced stability and targeting

Integration into siRNA and ASO payloads

Ionizable Lipid Synthesis for tailored delivery

Large-scale synthesis of proprietary ionizable lipids

Analytical characterization to confirm lipid identity and purity

Compatibility assessment with different oligonucleotide modalities

Novel carrier design and optimization

Request Customized Oligonucleotide Design Consultation

REsearch and Application

Conjugation Chemistry Expertise

Medicilon has successfully developed multiple conjugation chemistries to synthesize AOCs

Conjugation Methods
Antibody-C16-siRNA Conjugation
Antibody-siRNA Conjugation
Characterization of DAR 2 AOC

Multiple Conjugation Methods

Click Chemistry (DBCO-Azide)

Maleimide-Thiol Conjugation (MTC)

Amino-Oligo-Antibody Conjugation (AOAC)

Site-Specific Conjugation (SSC) via microbial transglutaminase (mTG nase)

Antibody-C16-siRNA Conjugation (Before Annealing) demonstrated precise conjugation techniques

Antibody-siRNA Conjugation (After Annealing) exhibited optimized post-annealing processes for enhanced stability

Scalability to produce high-purity AOCs

*15 mg target compound was obtained with a purity of 93 % by SEC

AOCs Characterization and DAR control:
- Advanced purification (AEX, SEC, LC-MS)
- Rigorous DAR (Drug-to-Antibody Ratio) control and verification

Characterization of DAR 2 AOC

The peak at 5.77 min corresponds to the AOC
The peak at 7.59 min corresponds to the free ASO

The AOC peak at 5.77 min is mainly composed of the DAR 2 species, with minimal amounts of other DAR variants present

Schedule a Technical Discussion with Our Chemist

Bioanalysis and Preclinical Evaluation

Medicilon’s bioanalytical services provide comprehensive support for AOC development, with advanced tools for large molecule analysis.

We ensure accurate and reliable data to support AOC development and regulatory submissions.

LC-MS/MS Analysis

Quantification of antisense (AS) and sense (SS) strands in plasma and liver tissues, as demonstrated in our Cyno Monkey PK study of siRNA

ELISA and Flow Cytometry

Tools like CTL ELISOPT Reader, CytofLEX S Flow Cytometer, and Beckman VI-CELL Cell Analyzer for precise bioanalysis

Metabolite Quantification

Identification and quantification of major metabolites in plasma and liver, ensuring thorough pharmacokinetic profiling

Global Clinical Support

In vitro and in vivo screening, preclinical GLP PK assays, and support for generic bioequivalence (BE) trials

Capabilities

Preclinical Evaluation Capabilities

Medicilon offers extensive preclinical capabilities for AOC and ADC development, supporting IND and NDA approvals. Key features include:

GLP & Non-GLP Toxicology StudiesSingle/multiple dose toxicity, reproductive toxicity, genotoxicity, carcinogenicity, and immunogenicity studies
Pharmacokinetic (PK) and Toxicokinetic (TK) Studies
Cyno Monkey ADC PK StudySingle-dose IV at 1 MPK, with serum and plasma collection up to 336 hours, analyzed via ELISA and LC-MS/MS
Balb/c Nude Mouse ADC PK StudySingle-dose IV at 10 MPK, with serum, plasma, and tumor tissue analysis using ELISA and LC-MS/MS
Monkey Plasma and Liver PK Study of siRNADose-dependent exposure analysis with no gender differences, supporting dose range studies (1-10 mg/kg)

Get a Preclinical Evaluation Plan for Your AOC

Animal Model Capacity:

Species

Rooms

Maximum Number

65 2,260

71 1,800

Rabbit

13

570

Rodent

94 24,100

Mini-pig

10

200

IND Approvals: Supported 27 ADC preclinical packages for IND/NDA, including PK, PD, and GLP toxicology studies for anticancer indications.

Let Medicilon help you to advance your AOC development

Contact Medicilon to leverage our expertise in RNAi discovery, conjugation chemistry, bioanalysis, and preclinical evaluation.

START YOUR AOC PROJECT- CONTACT US TODAY

Frequently Asked Questions

Have questions about AOC Studies?

Have more questions? Reach out to our experts.

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What are antibody oligonucleotide conjugates (AOCs)?

Antibody oligonucleotide conjugates (AOCs) are next-generation hybrid therapeutics that combine a targeting antibody with an oligonucleotide payload – such as siRNA or antisense oligonucleotides (ASOs) – to enable cell-type-specific gene modulation. Within an advanced AOC platform, these conjugates are designed to overcome key challenges in oligonucleotide delivery, including inefficient cellular uptake, limited tissue targeting, and degradation by nucleases.

What types of oligonucleotide payloads are supported in the Medicilon AOC platform?

The Medicilon AOC platform supports a wide range of therapeutic oligonucleotide payloads, including siRNA, antisense oligonucleotides (ASOs), and other emerging oligonucleotide formats. These payloads can be further optimized using backbone, sugar, and nucleobase modifications to enhance stability, potency, and safety in antibody oligonucleotide conjugates.

How does Medicilon optimize oligonucleotide chemistry for antibody oligonucleotide conjugates?

Medicilon optimizes oligonucleotide chemistry for antibody oligonucleotide conjugation through in-house mononucleotide synthesis and a proprietary library of more than 80 unique monomers. This enables flexible sequence design, custom nucleobase analogs, backbone modifications to extend half-life, and sugar modifications to improve binding affinity while reducing off-target effects.

What is the Medicilon Optimal Design (MOD) platform and how does it support AOCs?

The Medicilon Optimal Design (MOD) platform is a targeted oligonucleotide sequence design engine used within the AOC platform to improve gene-silencing efficacy. By applying focused-range prediction models, the MOD platform enables rational optimization of both sequence and chemistry, balancing potency, specificity, and developability for antibody oligonucleotide conjugates.

Does Medicilon offer GalNAc and ionizable lipid solutions for AOC delivery?

Yes. Medicilon provides a comprehensive GalNAc ligand library and custom linker designs that can be integrated into siRNA and ASO payloads used in antibody oligonucleotide conjugates. In addition, the company develops proprietary ionizable lipids at scale and evaluates their compatibility with different oligonucleotide modalities to support tissue-specific delivery strategies.

What antibody oligonucleotide conjugation chemistries are available?

Medicilon has established multiple antibody oligonucleotide conjugation strategies, including click chemistry (DBCO-azide), maleimide-thiol coupling, amino-oligo–antibody conjugation, and site-specific enzymatic conjugation using microbial transglutaminase. These approaches allow precise control of conjugation sites, linker architecture, and drug-to-antibody ratio (DAR).

How is drug-to-antibody ratio (DAR) controlled and characterized in AOCs?

DAR in antibody oligonucleotide conjugates is tightly controlled and characterized using advanced analytical techniques such as anion-exchange chromatography (AEX), size-exclusion chromatography (SEC), and LC-MS. Medicilon has demonstrated well-defined DAR species, including DAR 2 AOCs, with clear separation from free oligonucleotide, ensuring consistent conjugation profiles.

Can the Medicilon AOC platform support scale-up for preclinical studies?

Yes. The Medicilon AOC platform supports scalable production of antibody oligonucleotide conjugates, including multi-milligram synthesis with high purity suitable for preclinical studies. Process development and purification workflows are designed to be translatable from early discovery through IND-enabling supply.

What bioanalytical methods are available for AOCs and oligonucleotide payloads?

Medicilon offers a comprehensive bioanalytical toolkit for antibody oligonucleotide conjugates, including LC-MS/MS methods for quantifying antisense and sense strands in plasma and tissues. Additional assays such as ELISA, flow cytometry, and metabolite profiling are used to assess exposure, target engagement, and biotransformation.

Does Medicilon provide in vivo pharmacology and toxicology support for AOCs?

Medicilon supports both in vitro and in vivo pharmacology and toxicology studies for antibody oligonucleotide conjugates, including non-GLP and GLP PK studies and large-animal evaluations. These services are aligned with IND and NDA submission requirements for AOC and ADC-like modalities.

How does Medicilon’s ADC experience benefit antibody oligonucleotide conjugate development?

With extensive experience supporting ADC programs through IND and NDA, Medicilon applies proven expertise in conjugation chemistry, DAR control, PK/PD evaluation, and GLP toxicology to antibody oligonucleotide conjugates. This background helps de-risk CMC, bioanalysis, and safety packages within the AOC platform.

When should sponsors engage Medicilon for an AOC program?

Sponsors can engage Medicilon at any stage of antibody oligonucleotide conjugate development – from early sequence design and monomer chemistry through candidate selection, preclinical PK/PD, toxicology, and IND-enabling studies. The integrated AOC platform enables seamless support across the full development lifecycle.

Can conjugation strategies and linker designs be customized for specific AOC targets?

Yes. Medicilon customizes antibody selection, conjugation strategy, and linker design based on target biology and tissue distribution. This includes optimization of GalNAc linkers, ionizable lipids, and other carriers to enhance targeting efficiency and manufacturability of antibody oligonucleotide conjugates.

What regulatory and geographic support does Medicilon provide for AOC programs?

Medicilon provides global preclinical and clinical support, including GLP bioanalytical assays and data packages suitable for regulatory submissions across multiple regions. The team has experience supporting international regulatory strategies for complex biologic-oligonucleotide modalities.

How can we start a collaboration using the Medicilon AOC platform?

To initiate a collaboration, prospective partners can contact Medicilon through the website’s inquiry or business development channels. The team typically proposes a phased development plan covering oligonucleotide design, antibody oligonucleotide conjugation, bioanalysis, and preclinical evaluation tailored to the program’s objectives.

Our ADME/DMPK studies are aligned with global regulatory requirements, providing robust data for successful IND/NDA submissions.