Advanced AOCs Solutions for Biotechnology Innovation

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.
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.

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: 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

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

REsearch and Application

Conjugation Chemistry Expertise

Medicilon has successfully developed multiple conjugation chemistries to create AOCs

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

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:

Animal Model Capacity:

Species
Rooms
Maximum Number
65
2,260
71
1,800
13
570
94
24,100
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.

Contact Medicilon

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