Custom Antibody-Oligonucleotide Conjugation Service
Introduction to Antibody-Oligonucleotide Conjugates (AOCs)
Building on the success of antibody-drug conjugates (ADCs), which masterfully deliver potent payloads to diseased cells, AOCs represent the next evolutionary leap in precision medicine. While ADCs have revolutionized cancer therapy, their cytotoxic payloads can still pose risks of off-target toxicity. AOCs mitigate this by replacing these payloads with highly specific oligonucleotides, shifting the therapeutic paradigm from broad "cell killing" to precise "gene regulation."
This versatile platform typically utilizes one of several classes of oligonucleotides:
- siRNA (small interfering RNA): To achieve potent, targeted gene silencing.
- ASO (antisense oligonucleotides): To modulate RNA splicing or degradation.
- Aptamers: Where the oligonucleotide itself acts as a targeting or therapeutic agent.
This synergistic combination leverages the long half-life and exquisite specificity of an antibody to overcome the primary challenges of oligo-based therapies—namely, poor stability and inefficient tissue penetration. The result is a highly selective and potentially safer class of therapeutics capable of silencing the specific genes that drive disease.
Advanced Conjugation Chemistries
The creation of a stable and effective AOC depends entirely on the chemical strategy used to link the antibody to the oligonucleotide. The goal is to produce a homogenous, well-defined conjugate that retains the full biological activity of both components. Creative Biolabs is proficient in a comprehensive range of conjugation methods, allowing us to tailor the approach to your specific antibody, oligonucleotide, and research goals.
Fig.1 General methods to conjugate antibodies with oligonucleotides.1
Random Conjugation
These foundational methods target common amino acid residues. While effective for many applications, they can produce heterogeneous mixtures.
- Amine Coupling: Targets abundant lysine residues on the antibody surface using NHS-ester chemistry.
- Thiol Coupling: Targets cysteine residues. This often requires the reduction of native disulfide bonds, which must be carefully controlled to maintain the antibody's structural integrity.
Site-Specific Conjugation
Transformative Applications
AOCs are enabling breakthroughs across the life sciences, from fundamental research to late-stage clinical development. The versatility of this platform allows it to be adapted for a wide range of high-value applications.
- Targeted Therapeutics: This is the most significant application of AOCs. By delivering payloads like siRNA or ASOs directly to diseased cells, AOCs can silence the genes responsible for conditions such as rare genetic disorders, cancers, and neurological diseases. This targeted approach maximizes efficacy while minimizing off-target side effects.
- Ultra-Sensitive Diagnostics: The oligonucleotide portion of an AOC can serve as an amplifiable reporter tag. This is the principle behind Immuno-PCR (iPCR), a technique that can detect protein biomarkers at concentrations thousands of times lower than a conventional ELISA.
- Super-Resolution Imaging: In advanced microscopy techniques like DNA-PAINT, an oligo-labeled antibody is used to achieve imaging resolution at the single-molecule level, allowing researchers to visualize cellular machinery in unprecedented detail.
The potential applications for custom AOCs are continually expanding. If you have a novel application in mind, our R&D team is ready to collaborate with you to turn your concept into a reality.
Our Custom Conjugation Services
At Creative Biolabs, we provide a comprehensive, end-to-end solution for custom AOC development and production. We understand that each project is unique, and we offer a tailored suite of services designed to meet your specific needs, from early-stage discovery to preclinical manufacturing.
Strategic Consultation
We begin every project with a deep-dive consultation to understand your goals and design the optimal AOC construct, including antibody selection, oligonucleotide design, and conjugation strategy.
Oligonucleotide Synthesis & Modification
We provide high-quality synthesis of your custom oligonucleotide sequence, including any required chemical modifications, functionalization for conjugation, and lipid additions.
Antibody Sourcing & Modification
We can work with an antibody you provide or source and modify a specific antibody for your project. This includes fragmentation and engineering for site-specific conjugation.
Process Development & Optimization
Our scientists develop and optimize the conjugation reaction to ensure high efficiency, yield, and the desired oligo-to-antibody ratio.
Purification & Characterization
Every AOC we produce undergoes rigorous purification to remove unconjugated materials. We then provide a full analytical characterization package, including techniques like HPLC and Mass Spectrometry, to confirm the identity, purity, and integrity of the final product.
Workflow
The transformative potential of Antibody-Oligonucleotide Conjugates is clear. Partnering with an experienced team is the key to unlocking that potential for your program. At Creative Biolabs, we combine two decades of bioconjugation expertise with a commitment to quality and collaboration to accelerate your research. Contact our technical team today to request a quote and discuss how our custom AOC services can advance your next breakthrough.
Reference
- Dugal-Tessier, Julien et al. "Antibody-Oligonucleotide Conjugates: A Twist to Antibody-Drug Conjugates." Journal of Clinical Medicine vol. 10,4 838. 18 Feb. 2021, doi:10.3390/jcm10040838. Under an open access license CC BY 4.0, without modification.