Custom Protein-Oligonucleotide Conjugation Services
Introduction
The fusion of proteins and oligonucleotides creates powerful chimeric molecules that merge the functional diversity of proteins with the programmability of nucleic acids. This synergy has unlocked significant advancements across biotechnology. As detailed in recent scientific reviews, the ability to create these conjugates in a controlled manner is fundamental to their application. Success hinges on choosing the correct conjugation strategy to produce a well-defined, functional product, enabling breakthroughs in areas from targeted therapeutics to ultrasensitive molecular diagnostics and the assembly of complex nanoarchitectures.
Strategies for Protein-Oligonucleotide Conjugation
The choice of method is critical for achieving the desired specificity and preserving protein function. Key approaches include:
- Chemical Methods Targeting Native Residues: These foundational techniques utilize the inherent reactivity of naturally occurring amino acids. Common strategies include targeting the primary amines of lysine residues with N-hydroxysuccinimide (NHS) esters or the sulfhydryl groups of cysteine residues with maleimides.
- Bioorthogonal Chemistry with Non-Native Handles: To achieve absolute site-specificity, unnatural amino acids (UAAs) containing unique chemical handles (e.g., azides, alkynes, ketones) can be incorporated into the protein. These handles enable highly selective, bioorthogonal reactions like click chemistry (CuAAC, SPAAC) or oxime ligation, which proceed with high efficiency under mild conditions.
- Biochemical and Enzymatic Ligation: This approach uses enzymes for precise, site-specific conjugation.
Fig.1 Chemical strategies for protein-oligonucleotide conjugation.1
Application of Protein-Oligonucleotide Conjugates
- Therapeutics: Serve as targeted drug delivery systems, using antibodies to deliver oligonucleotide payloads (e.g., siRNA, aptamers) to specific cells.
- Diagnostics: Enable ultra-sensitive detection platforms like immuno-PCR for detecting biomarkers at femtomolar levels.
- Nanotechnology: Act as critical components for the programmed assembly of protein arrays and the construction of functional DNA origami nanostructures.
How Can We Assist Your Project
At Creative Biolabs, we transform the complexity of bioconjugation into a streamlined, reliable solution for your research. We specialize in designing and executing bespoke conjugation strategies that yield precisely defined, active, and highly pure protein-oligonucleotide conjugates tailored to your specific application. Our service moves beyond standard, one-size-fits-all methods to provide a consultative partnership, ensuring the final conjugate possesses the exact stoichiometry, stability, and functionality required for your project's success, whether it be for advanced therapeutics, diagnostics, or materials science.
Types of our Service
Peptide-Oligonucleotide Conjugation
We conjugate synthetic peptides with oligonucleotides, including DNA, RNA, and nucleic acid analogs like PNAs. This service is ideal for creating tools for cellular delivery, molecular probes, and self-assembling nanomaterials.
Antibody-Oligonucleotide Conjugation
Our service focuses on producing highly defined antibody-oligonucleotide conjugates (AOCs) for applications in targeted therapy and advanced diagnostics.
Enzyme-Oligonucleotide Conjugation
We conjugate active enzymes to oligonucleotides for applications in diagnostics (e.g., immuno-PCR, ELISA) and biocatalysis.
Workflow
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Required Starting Materials:
- Purified protein (e.g., >1 mg of antibody at >95% purity) with detailed buffer composition, concentration, and formulation data.
- Oligonucleotide sequence, including any required modifications (e.g., 5'-Thiol C6, 3'-Azide), purity specifications, and quantity.
- Project goals, including the intended application of the final conjugate and any specific performance requirements.
- Key Steps Involved:
| Step | Description |
|---|---|
| Consultation & Strategic Design | We begin with a thorough technical consultation to understand your project objectives. Our experts then design a tailored conjugation strategy, selecting the optimal chemistry, linker, and purification method. |
| Biomolecule Modification & Activation | The protein and/or oligonucleotide are chemically modified to introduce the necessary reactive functional groups. This step is performed under controlled conditions to maintain biomolecule integrity. |
| Conjugation Reaction & Optimization | The activated protein and oligonucleotide are reacted under optimized conditions (e.g., pH, temperature, molar ratios) to maximize conjugation efficiency and yield of the desired conjugate. |
| Purification of the Conjugate | The final conjugate is purified from unreacted starting materials and byproducts using advanced chromatography techniques, such as Size Exclusion (SEC) or Ion-Exchange (IEX) HPLC. |
| Quality Control and Analysis | The purified conjugate undergoes rigorous quality control testing to confirm its identity, purity, and integrity. |
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Final Deliverables:
- The final, purified protein-oligonucleotide conjugate at the agreed-upon quantity and concentration.
- A comprehensive Certificate of Analysis (CoA) including SEC-HPLC data to demonstrate purity and aggregation state.
- Mass Spectrometry analysis confirming the successful conjugation and final molecular weight.
- Estimated Timeframe: The typical timeframe for a standard conjugation project ranges from 4 to 8 weeks. This can vary depending on the complexity of the chosen strategy, the need for custom synthesis of components, and the scale of the project.
Why Choose Us?
Choosing Creative Biolabs means choosing a partner dedicated to precision, innovation, and the success of your project. Unlike services that rely solely on standard, non-specific chemistries, we offer a comprehensive suite of cutting-edge, site-specific conjugation technologies. Our deep expertise allows us to tackle the most complex conjugation challenges, ensuring the production of homogeneous, highly functional molecules that deliver superior performance and reproducibility. We are committed to providing not just a product, but a scientifically robust solution that accelerates your research and development.
Customer Reviews
"Using Creative Biolabs' Custom Protein-Oligonucleotide Conjugation Service in our research has significantly improved our therapeutic antibody development. The resulting conjugate was incredibly homogeneous, which has been critical for our IND-enabling studies."
— Dr. Elaor Rdey [May 2025]
"We needed to conjugate an enzyme to an oligonucleotide without losing its function. The final conjugate Creative Biolabs delivered showed high purity and maintained excellent enzymatic activity, which was crucial for our diagnostic application. The consistency between batches was also very reliable."
— Mcus Wtnabe [February 2025]
"Using Creative Biolabs' Custom Protein-Oligonucleotide Conjugation Service in our research has significantly improved our work on synthetic molecular systems. The technical support was outstanding. They designed a multi-step strategy using orthogonal protecting groups and chemistries that worked flawlessly."
— Dr. Smntha Chn [November 2024]
FAQs
Will the conjugation process affect my protein's activity?
A: This is a primary concern and a key focus of our service. Our emphasis on site-specific conjugation is designed to minimize any impact on protein function. By targeting regions distant from active sites or antigen-binding domains, and by using milder, bioorthogonal chemistries, we maximize the retention of your protein's biological activity.
What is the typical scale for a custom conjugation project?
A: We are equipped to handle projects ranging from initial proof-of-concept studies at the 1-2 mg scale to larger preclinical productions of 100+ mg. We encourage you to discuss your specific needs with our team, as we can tailor the project scope to fit your goals and budget.
How stable are the final protein-oligonucleotide conjugates?
A: The stability of the linkage is a critical design parameter. We select chemistries that produce highly stable covalent bonds (e.g., amide bonds, thioethers) designed to withstand physiological conditions. For applications requiring reversible linkages, we can also design conjugates with cleavable linkers (e.g., disulfide bonds). Each conjugate is delivered with recommended storage conditions to ensure long-term stability.
What makes your service different from a standard conjugation kit or CRO?
A: While kits and standard services offer a one-size-fits-all approach, we provide a fully customized, consultative solution. We don't just perform a reaction; we design a complete strategy. Our access to a wide array of advanced, site-specific technologies allows us to successfully conjugate challenging proteins and produce highly homogeneous materials that are often unattainable with standard methods.
Related Services
Custom Oligonucleotide Synthesis
High-quality DNA, RNA, and modified oligonucleotides synthesized to your specifications, ready for conjugation.
High-purity synthetic peptides with a wide range of modifications, purities, and scales to support your research.
Recombinant Protein Production
Expression and purification of your target protein, from bacterial to mammalian systems, ensuring a high-quality starting material for your project.
Custom Antibody Production
Development of monoclonal or polyclonal antibodies tailored to your needs, providing the perfect targeting moiety for your conjugate.
How to Contact Us
At Creative Biolabs, we are your dedicated partners in building the next generation of advanced biomolecules. Our Custom Protein-Oligonucleotide Conjugation Service provides the expert strategy, cutting-edge technology, and rigorous quality control needed to bring your most ambitious projects to life.
Ready to discuss your project? Our team of conjugation specialists is here to help you design the optimal strategy for your research. Contact us for more information.
Reference
- Watson, Emma E, and Nicolas Winssinger. "Synthesis of Protein-Oligonucleotide Conjugates." Biomolecules vol. 12,10 1523. 20 Oct. 2022, doi:10.3390/biom12101523. Under an open access license CC BY 4.0, without modification.