We specialize in the efficient and stable conjugation of single or double-stranded oligonucleotides to full antibodies or antibody fragments, crucial for targeted delivery and advanced diagnostic applications.
Standing at the forefront of innovation, Creative Biolabs offers core oligonucleotide conjugation services, specializing in the precise linkage of oligonucleotides to antibodies and a wide range of proteins. With advanced proprietary technologies and a deep understanding of bioconjugation chemistry, we empower our clients to overcome critical challenges in drug delivery, diagnostics, and fundamental research, delivering high-performance conjugates with unparalleled specificity and efficacy.
Introduction to Oligonucleotide Conjugation
Oligonucleotide-based therapeutics and diagnostics hold immense promise, yet their clinical translation has historically been hampered by inherent limitations. Challenges such as inadequate pharmacokinetic properties, enzymatic degradation, and inefficient cellular uptake often impede their journey from bench to bedside. Covalent linkage to various carefully selected ligands presents a transformative solution. By strategically conjugating oligonucleotides to molecules that specifically target certain tissues, enhance cellular internalization, or modulate biological distribution, we can significantly advance their therapeutic and diagnostic applications. Notably, the creation of oligonucleotide-antibody conjugates offers a supremely efficient and precise avenue for detecting low-abundance proteins, making this approach indispensable across diverse diagnostic and therapeutic pipelines. This synergistic fusion unlocks new functionalities, paving the way for more targeted and potent molecular tools.
Fig 1. Oligonucleotide-antibody conjugation.1,3
Oligonucleotide Conjugation Services Provided by Creative Biolabs
At Creative Biolabs, we offer comprehensive and cutting-edge oligonucleotide conjugation services designed to meet the rigorous demands of modern biomedical research and development. Our expertise encompasses the entire process, from initial design consultation to the delivery of meticulously characterized, high-purity conjugates, ensuring seamless integration into your research workflows.
Our skilled scientists leverage state-of-the-art facilities and a deep understanding of bioconjugation chemistry to generate conjugates with exceptional precision. We can provide custom conjugates ranging from milligram to gram scales, consistently maintaining your desired antibody: oligonucleotide ratio with high reproducibility. Beyond standard requests, we are adept at handling complex projects, including dual conjugation strategies and novel ligand pairings.
Our services are meticulously tailored to your specific project requirements, encompassing:
Antibody-Oligonucleotide Conjugation
Protein-Oligonucleotide Conjugation
Beyond antibodies, our capabilities extend to conjugating oligonucleotides with a diverse array of other proteins, such as enzymes, receptors, or structural proteins, creating novel functional bioconjugates.
Custom Ligand Conjugation
For highly specialized applications, we offer conjugation services for a broad spectrum of customized ligands, including:
- Peptides: For enhanced cellular penetration, stability, or specific targeting.
- Carbohydrates: To enable tissue-specific targeting, particularly to liver cells (e.g, GalNAc).
- Aptamers: For novel sensing and therapeutic applications, leveraging their unique binding properties.
- Small Molecules: Including fluorophores, biotin, or therapeutic agents, for specific detection, affinity capture, or targeted drug delivery.
Comprehensive Validation and Characterization
Beyond delivering the highest purity conjugates, we possess the in-house capability to undertake rigorous validation of biochemical parameters, detailed analysis of uptake mechanisms, and preliminary assessment of pharmacokinetic characteristics, providing you with a holistic understanding of your conjugate's performance.
Applications of Oligonucleotide Conjugation
Targeted Drug Delivery
By conjugating therapeutic oligonucleotides (e.g, siRNAs, ASOs, aptamers) to antibodies or cell-penetrating peptides, we enable highly specific delivery to diseased cells or tissues, minimizing off-target effects and enhancing therapeutic windows for cancer, genetic disorders, and infectious diseases.
High-Sensitivity Diagnostics
Oligonucleotide-antibody conjugates are pivotal in developing ultrasensitive diagnostic assays like immuno-PCR (iPCR), significantly boosting the detection limits for biomarkers, pathogens, and low-abundance proteins, surpassing traditional ELISA methods.
Molecular Imaging & Probes
Attaching fluorescent dyes, radioactive labels, or magnetic nanoparticles to oligonucleotides creates sophisticated probes for real-time in vitro and in vivo imaging, facilitating the visualization of gene expression, protein localization, and cellular processes.
Gene Editing & Silencing
Conjugated guide RNAs or antisense oligonucleotides can be precisely delivered to specific cellular compartments, improving the efficiency and specificity of gene editing and gene silencing strategies.
Biosensors & Aptasensors
Oligonucleotide conjugates form the basis of highly selective biosensors for detecting a wide range of analytes, from small molecules to proteins, leveraging the unique binding capabilities of aptamers for diagnostic and environmental monitoring.
Immuno-Oncology
Novel conjugates can act as immune modulators or enhance the delivery of immunotherapeutic agents, opening new avenues for cancer treatment by specifically targeting immune cells or tumor microenvironments.
Published Data
Title: Non‑specific interactions of antibody‑oligonucleotide conjugates with living cells
Research Objective:
The research aims to observe the impact of hydrophilic and charged payload conjugation on antibody functionality, particularly the alterations in binding affinity and cell selectivity post-antibody-oligonucleotide conjugation.
Research Methods:
Researchers synthesized a series of fluorescein-labeled single-chain and double-chain antibody-oligonucleotide conjugates. Time-resolved analysis using ligand binding assays was employed to evaluate the interaction of conjugates with specific cell lines MDA-MB-231 (HER2−) and SK-BR-3 (HER2+).
Research Findings:
Research findings indicate that oligonucleotides represent a particularly effective payload, potentially influencing their binding characteristics post-antibody conjugation. Conjugation of single-chain oligonucleotides with proteins induces non-specific interactions consistent with the cell surface, whereas double-chain oligonucleotides exhibit minimal impact. Therefore, in the development of antibody-oligonucleotide conjugates for various applications, careful consideration of their structure and preparation strategy is imperative.
Fig.2 Association rate constants.2, 3
Features of Our Services
- Professional Expertise: Every conjugation project is meticulously executed by our team of highly experienced scientists, ensuring precision, reliability, and adherence to the highest scientific standards.
- Flexible Service Options: We offer fully customizable conjugation ratios and scales, allowing for precise tailoring to your unique research demands, from discovery-phase microgram quantities to larger preclinical batches.
- Expedited Turnaround: Our optimized workflows and dedicated resources enable a remarkably short duration from project initiation to conjugate delivery, accelerating your research timelines without compromising quality.
- Exceptional Reproducibility: Our rigorously validated protocols ensure that conjugates are consistently generated with high purity and defined ratios, making them applicable across diverse protein types and experiments.
- Integrated Technical Support: We provide comprehensive technical support throughout the entire project lifecycle, from initial consultation and experimental design to post-delivery characterization and troubleshooting.
Q&A
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Q: What types of oligonucleotides can be conjugated using your service?
A: We are equipped to handle a wide range of oligonucleotide types for conjugation. This includes DNA oligonucleotides, RNA oligonucleotides, various forms of modified RNA such as siRNA (small interfering RNA), and aptamers. Furthermore, we can work with oligonucleotides containing specific modifications that enhance their stability or enable particular conjugation chemistries.
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Q: How do you ensure the stability of the conjugated product?
A: Ensuring conjugate stability is paramount for reliable downstream applications. We achieve this through careful selection of robust conjugation chemistries, such as stable amide bonds or thioether linkages, that are resistant to enzymatic degradation and varying physiological conditions. Additionally, our rigorous purification and characterization steps remove unstable side products, contributing to the overall stability of the final conjugate.
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Q: What quality control (QC) measures are in place for the conjugated products?
A: Our conjugated products undergo a multi-faceted QC process to guarantee their purity and structural integrity. Key analytical techniques include Mass Spectrometry (MS) for verifying the molecular weight and successful conjugation, High-Performance Liquid Chromatography (HPLC) for assessing purity and homogeneity, and gel electrophoresis (PAGE) for confirming the conjugate's size and integrity.
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Q: Can I request a specific oligonucleotide-to-antibody ratio for my conjugate?
A: Absolutely, we offer highly customizable conjugation services to meet your precise experimental requirements. You can specify your desired oligonucleotide-to-antibody ratio, and our expert scientists will employ optimized protocols to achieve that ratio. This flexibility allows for fine-tuning the biological activity and delivery efficiency of your conjugate.
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Q: Do you offer any support for the downstream application of the conjugates?
A: Our commitment extends beyond simply delivering the conjugate. We offer comprehensive technical support and consultation throughout your project. Our scientific team can provide guidance on storage conditions, recommendations for initial testing in your specific application, and troubleshoot any issues you might encounter during the experimental phase.
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Q: Can you help with the design of the oligonucleotide or the linker chemistry?
A: Yes, we provide thorough help from the very beginning of your project. Our experienced scientists can provide expert consultation on oligonucleotide design, including considerations for sequence optimization and appropriate modifications, to enhance conjugation efficiency and stability. We can also advise on the optimal linker chemistry tailored to your specific application and the nature of your target molecule.
Supported by a team of scientists and experts in the field of IVD antibody development, Creative Biolabs offers globally integrated antigen and antibody conjugation services to meet the specific requirements of each client. With rich experience and advanced technologies, we aim to provide oligonucleotide conjugation services in the most optimal and cost-effective manner.
If you are interested in our services and would like more detailed information, please feel free to contact us for personalized technical support. Our project managers will promptly connect with you to help design a tailored solution to meet your specific needs.
References
- Dugal-Tessier, Julien, Srinath Thirumalairajan, and Nareshkumar Jain. "Antibody-oligonucleotide conjugates: a twist to antibody-drug conjugates." Journal of Clinical Medicine 10.4 (2021): 838.
- Lehot, Victor, et al. "Non-specific interactions of antibody-oligonucleotide conjugates with living cells." Scientific Reports 11.1 (2021): 5881.
- Distributed under Open Access license CC BY 4.0, without modification.
For Research Use Only.
