Antibody-Oligonucleotide Conjugates (AOCs)
Monoclonal Antibody (mAb)
- Description: It has high affinity and specific targeting for receptors or antigens expressed on the surface of diseased cells (e.g., tumor cells, immune cells, or cells in fibrotic tissue).
- Function: Determines biodistribution and cellular internalization pathways.
Oligonucleotide (ON)
- Description: The therapeutic payload, which can be small interfering RNA (siRNA), antisense oligonucleotide (ASO), microRNA (miRNA), or aptamers.
- Function: Its function is to regulate gene expression, for example, by inducing mRNA degradation or modifying precursor mRNA splicing.
Linker
- Description: A chemical linker group that connects the mAb and ON. The chemical properties, length, and cleavability (or incleavability) of the linker are crucial.
- Functions: They directly affect the stability of conjugates in circulation, the efficiency of ON release in target cells, and ultimately the therapeutic index.
Our Services
Creative Biolabs offers extensive AOC synthesis services to customers globally. With advanced synthesis technologies of siRNA, ASOs, and antibodies, we can assure the effectiveness of AOCs.
Ion Interactions-Based Conjugation
We achieve coupling by fusing or modifying antibodies to link polycationic fragments. This coupling method utilizes the interaction between positive and negative charges to ultimately bind to the oligonucleotide backbone.
This method is applicable to a variety of oligonucleotides because it allows for the simple and flexible coupling of different oligonucleotide sequences to a single polycationic protein. This enables us to use the same antibody to assess different gene knockdowns and detect their activity in cells.
Avidin-Based Conjugation
We prepare antibody-drug conjugates (AOCs) by utilizing the strong interaction between biotin-labeled oligonucleotides and avidin, or by using neutral avidin as a bridging group for the antibody.
One advantage of this method is the good in vivo stability of the resulting conjugates. It can target specific tissues for gene knockdown without causing systemic effects like in gene knockout mouse models, thus providing a more easily operable and widely applicable method for disease state modeling.
However, due to the multiple steps required, its versatility may not be as good as ion-interaction-based methods.
Direct Conjugation
We use a linker group, which is added to the oligonucleotide (ON) and immediately linked to a lysine, cysteine, or synthetic amino acid of the antibody.
This technique has the advantage of a smaller linker group and less impact on the overall conjugate compared to larger protamine or avidin complexes. Although there are no lysosomal escape agents, this can still lead to the gradual release of the oligonucleotide from the lysosome, potentially affecting the potency of the antiviral drug complex (AOC).
Nevertheless, due to its cost-effectiveness and speed, it is expected to become the preferred method for preparing AOCs in the future.
Hybridization Conjugation
We also use double-stranded oligonucleotides (e.g., conjugating a single-stranded oligonucleotide to an antibody and then hybridizing the complementary strand) to prepare AOCs.
The length of the oligonucleotide plays a crucial role in this hybridization process. If the oligonucleotide sequence is too short, the resulting double strand may lack stability in plasma; while if it is too long, it may lead to the formation of unwanted secondary structures.
For example, cetuximab can be used as a targeted drug to deliver doxorubicin, which can penetrate cells by intercalating into a double-stranded oligonucleotide.
Applications of AOCs
AOCs can be applied to medication delivery, immunotherapy enhancement, and biomarker detection to improve treatment efficacy and diagnostic sensitivity. They have been utilized for therapeutic purposes by carrying ASO or siRNA payloads and as a pretargeting component for both radionuclide therapy and imaging applications.
In these circumstances, the antibody targets the location of interest, where the coupled ONs may operate as a gene-silencing or pretargeted therapeutic agent. Figure 1 depicts the various applications of AOCs.
Our Technology Platform for Antibody-Oligo Conjugates Synthesis
At Creative Biolabs, our advanced data-driven AOC platform is designed to provide you with a seamless and efficient workflow from concept to high-quality drug candidates.
Unparalleled Efficiency
Our platform utilizes intelligent algorithms to optimize processes, significantly reducing time and achieving industry-leading yields, accelerating your projects.
Superior Product Quality
We focus on site-specific conjugation, providing highly homogeneous AOCs with precise drug-antibody ratios (DAR), low aggregation, and high purity.
Complete Bioactivity Preservation
Our unique technology ensures perfect coordination between the antibody's targeting function and the oligonucleotide's gene-regulatory activity.
Uncompromising QA
From sequence analysis to functional testing, we conduct comprehensive release testing on all critical quality attributes (CQA) to ensure safety and reliability.
End-to-End Services
We offer a seamless integrated workflow from antibody engineering and oligonucleotide synthesis to conjugation, analysis, and in vitro/in vivo validation.
Scalable Applications
Our process development is centered on translational applications. We employ scalable conjugation chemistry methods and stringent control strategies early on.
Instrumentation Platform for AOC Workflow
The synthesis of high-fidelity antibody-oligonucleotide conjugates (AOCs) is not merely a matter of chemical reaction processes, but a complex process entirely dependent on cutting-edge instrumentation.
Types of Antibody-Oligonucleotide Conjugates (AOCs)
| AOC Type | Oligonucleotide Payload | Mechanism of Action |
|---|---|---|
| AOC-siRNA | Small Interfering RNA | Gene Silencing - Induces degradation of target mRNA, preventing protein expression. |
| AOC-ASO | Antisense Oligonucleotide | RNA Modulation - Blocks translation, modulates pre-mRNA splicing (exon skipping/inclusion), or induces degradation. |
| AOC-Aptamer | Aptamer | Targeting/Therapeutic - The ON acts as the recognition element or interferes with protein function. |
| AOC for Diagnostics | DNA/Oligo Reporter Tag | Signal Amplification - Used in Immuno-PCR (iPCR) assays. |
Success Stories from Our Clients
"Creative Biolabs' precise delivery of the targeted AOC we needed was impressive. Its high homogeneity greatly simplified our in vivo studies, enabling us to obtain clearer and more promising efficacy data than previously possible using randomized methods."
Oncology Research Team
Oncology R&D
"Creative Biolabs' deep understanding of ASO chemistry and their ability to successfully conjugate our highly challenging mAb has brought a breakthrough to our central nervous system targeted therapy program. Functional data confirmed that both antibody binding capacity and ASO activity were fully preserved."
Gene Therapy Research Team
Gene Therapy
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Frequently Asked Questions
The ideal OAR depends on the specific circumstances. While a higher OAR can increase drug loading, it can also compromise antibody integrity or lead to aggregation, especially in the case of random conjugation. We typically employ a site-specific approach to achieve a lower and more stable OAR (e.g., 2-4) to ensure an optimal balance between payload delivery, conjugate stability, and antibody binding affinity.
Project lead time varies depending on the complexity of the conjugation chemistry and the required scale. A standard custom AOC synthesis project typically takes 8-12 weeks from consultation to final delivery, while more complex projects involving the development of novel linker chemistry take longer.
The standard lead time is 6-8 weeks after project design finalization, including antibody engineering (if necessary), oligonucleotide synthesis, conjugation, and comprehensive quality control.
Yes. We accept antibodies provided by our clients. The antibody concentration should be greater than 1 mg/mL, dissolved in a low-amine buffer (e.g., PBS), and the purity should be greater than 90% (as determined by SEC). We will conduct a feasibility assessment upon receiving the antibody.
Using our site-specific method, we can reliably obtain a uniform DAR of 1.0 or 2.0, depending on the engineering strategy. For random conjugations (if required), the DAR is typically distributed between 2 and 4.
Our AOCs are highly stable. We recommend storing them in nuclease-free neutral buffer at 4°C or -20°C. Specific storage recommendations and stability data are provided for each conjugate.
Connect with Us Anytime!
Antibody-Oligo Conjugates are more than just a novel reagent; they represent a fundamental shift in how we interrogate biological systems. By digitally encoding protein information, they have seamlessly integrated proteomics into the scalable, high-throughput world of sequencing.
As we look to the future, the role of AOCs will only expand, finding applications in targeted oligonucleotide delivery for gene therapy, increasingly complex multi-omic panels, and as critical components of new in vitro diagnostics.
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