What types of oligonucleotides can be used for conjugation?

We support siRNA, ASOs, DNA, RNA, aptamers, and other customized oligonucleotide scaffolds. Modification sites and conjugation routes are selected based on sequence length, backbone chemistry, and downstream use.

Which conjugation chemistry is best for my project?

The optimal chemistry depends on your molecule type, target site, conjugation partner, and whether you need site specificity, cleavable linkers, or strong biocompatibility. Click chemistry is often preferred for mild and selective reactions, while thiol-maleimide coupling remains widely used for thiol-containing systems.

Can you help improve cellular uptake or biodistribution?

Yes. Modules such as cholesterol, PEG, peptides, polymers, and selected small-molecule ligands can be introduced to improve uptake, tissue distribution, or in vivo stability.

How do you confirm successful conjugation and product quality?

We use orthogonal analytical methods such as HPLC/UPLC, LC-MS, CE, UV-Vis, and, where needed, DLS to confirm molecular weight, purity, conjugation efficiency, and stability.

Can you work with customer-supplied oligonucleotides or ligands?

Yes. We support both customer-supplied materials and de novo synthesis. Project feasibility is evaluated based on structure, purity, solubility, and reactive group status.

What factors most affect project success?

Important factors include modification site selection, linker design, chemical compatibility, reaction-induced aggregation risk, and purification efficiency. These are evaluated during early-stage project design.

Nucleic Acid/Oligonucleotide Conjugation Services

Peptide Bioconjugation

Fluorescent Bioconjugation

Bead & Particle Bioconjugation

Small Molecule Bioconjugation

PEGylation Bioconjugation

Cyclodextrin Bioconjugation

Aptamer Bioconjugation

Cholesterol Bioconjugation

Nanoparticle Bioconjugation

Folic Acid Bioconjugation

DPC Bioconjugation

CpG Bioconjugation

Creative Biolabs provides Nucleic Acid/Oligonucleotide Conjugation Services for researchers developing targeted delivery systems and diagnostic probes.

By combining sequence-defined oligonucleotides with functional payloads, conjugation can improve serum stability, circulation time, cellular uptake, and analytical signal output.

Project success often depends on selecting the right modification site, linker design, and analytical characterization strategy. We tailor each project based on molecule type and application goals.

Scientific visualization of oligonucleotide conjugation

Our Nucleic Acid and Oligonucleotide Conjugation Service

• Introduction of reactive groups at the 5′ end, 3′ end, or internal sites of oligonucleotides
• Available handles include amino, thiol, alkyne, azide, and other customized functional moieties
• Support for both solid-phase synthesis-based modification and post-synthetic derivatization
• Activation design for downstream maleimide-, NHS ester-, and click chemistry-based conjugation
• Rational attachment site selection to preserve activity while enabling efficient coupling

Oligonucleotide Modification & Activation

Conjugation Chemistry Development

• Customized route selection based on molecule type, partner, and end application
• Available strategies include click chemistry, thiol-maleimide coupling, amide coupling, and enzymatic ligation
• Optimization of pH, temperature, stoichiometry, solvent system, and reaction time
• Emphasis on selectivity, compatibility, yield, and product integrity

• Removal of free oligonucleotides, excess ligands, over-conjugated species, and aggregates
• Purification options include preparative or semi-preparative HPLC and SEC
• Separation workflows tailored to physicochemical properties and project scale
• Improved sample uniformity, recovery, and reproducibility

Purification & Separation

Characterization & Quality Evaluation

• Assessment of MW, purity, substitution ratio, structural integrity, and aggregation state
• Analytical tools include LC-MS, CE, UV-Vis, and DLS
• Orthogonal QC strategy to ensure final sample quality and conjugation success
• Comprehensive Certificate of Analysis (COA) provided to support your downstream research and evaluations

Structural & PK Modification

Optimizing Physiochemical Properties for Therapeutic Success

We specialize in sophisticated chemical modifications that overcome the inherent limitations of natural oligonucleotides. Our platform addresses core challenges such as rapid renal clearance and enzymatic degradation through site-specific PEGylation and lipid tailoring (e.g., cholesterol, DPC). By precisely controlling the density and position of these modifications, we achieve optimal pharmacokinetic profiles while maintaining target-binding potency.

Key advantages:Enhanced nuclease resistance, extended systemic half-life, and significantly improved aqueous solubility for lipophilic constructs.
Typical applications:Systemic delivery optimization for siRNA, ASOs, and mRNA, as well as fine-tuning biodistribution for antisense therapies.

• PEGylation Bioconjugation • Cyclodextrin Bioconjugation • Cholesterol Bioconjugation • DPC Bioconjugation

Targeting & Functional Conjugation

• Peptide Bioconjugation • Aptamer Bioconjugation • Folic Acid Bioconjugation • Small Molecule Bioconjugation • CpG Bioconjugation

Ligands for Precision Delivery

Precision delivery is the cornerstone of our functional conjugation strategies. We leverage high-affinity ligands—including cell-penetrating peptides (CPPs), tissue-specific aptamers, and small molecules like folic acid—to trigger receptor-mediated endocytosis. Our chemical expertise ensures that the conjugation process preserves both the ligand’s recognition capability and the oligonucleotide’s regulatory activity.

Key advantages:Superior cell-type specificity, reduced off-target toxicity, and enhanced intracellular bioavailability.
Typical applications:Development of next-generation AOCs (Antibody-Oligonucleotide Conjugates), tumor-targeted gene silencing, and precision immunomodulation.

Material, Carrier & Detection

Integrated Solutions for Diagnostics

Beyond in vivo therapeutic delivery, we provide robust solutions for immobilizing oligonucleotides onto diverse solid supports and carriers. Whether it’s functionalizing magnetic beads for high-efficiency sample capture or conjugating quantum dots and fluorescent dyes for ultra-sensitive bioimaging, we optimize the interface chemistry to minimize non-specific binding and maximize the signal-to-noise ratio.

Key advantages:High surface loading density, excellent colloidal stability, and versatile detection options (fluorescence, chemiluminescence).
Typical applications:IVD assay development, spatial biology probes, nanoparticle-based delivery vehicles, and advanced molecular sensing.

• Bead & Particle Bioconjugation • Nanoparticle Bioconjugation • Fluorescent Bioconjugation

Technology Platform for Oligonucleotide Conjugation

Creative Biolabs has established an end-to-end oligonucleotide conjugation platform covering synthesis, reaction development, purification, and analytical characterization.

Synthesis & Pretreatment Platform

Our automated oligonucleotide synthesizers support the preparation of high-purity oligonucleotides with customized lengths and terminal modifications. Vacuum concentrators are used for sample concentration and drying after purification, while automated buffer exchange systems support desalting and reaction condition matching before conjugation.

Reaction & Purification Platform

Temperature-controlled shaking reactors help maintain precise reaction conditions and kinetics. Preparative and semi-preparative HPLC systems are used for removing excess ligands and separating conjugate species with different loading levels. Advanced automated chromatography systems support SEC and affinity purification for complex conjugate systems.

Analytical & Characterization Platform

LC-MS is used for molecular weight confirmation, conjugation verification, and sequence integrity analysis. CE supports purity and charge heterogeneity analysis. UV-Vis can be used to estimate conjugation efficiency, while DLS monitors aggregation behavior and colloidal stability.

Oligonucleotide Conjugation Workflow

Our standard oligonucleotide conjugation workflow includes five key steps:

Consultation & Design

We define conjugation sites, linker options, and functional moieties based on your molecular format and intended application.

Reactive groups are introduced into the oligonucleotide, followed by pretreatment and optimization.

Oligonucleotide Modification

Optimized Conjugation

The conjugation reaction is performed under carefully controlled conditions, including pH, temperature, and stoichiometry.

The target conjugate is purified using HPLC, SEC, or TFF and characterized using orthogonal analytical tools.

Purification & Orthogonal QC

Delivery

We deliver high-purity, traceable, and application-ready conjugates with supporting documentation.

Applications of Nucleic Acid and Oligonucleotide Conjugation

Our nucleic acid/oligonucleotide conjugation services can be used in a wide range of research scenarios:

Delivery optimization and in vivo stability enhancement of siRNA, ASOs, aptamers, and other oligonucleotide therapeutics
Tumor-targeted, liver-targeted, or receptor-mediated delivery studies
Construction of AOCs, ODCs, and multifunctional oligonucleotide therapeutics
Development of IVD probes, capture probes, fluorescent probes, and barcode probes
Bioimaging, pharmacokinetic tracking, and cellular uptake studies
Functionalization of beads, nanoparticles, and surface-based carriers
High-throughput screening, spatial biology, molecular sensing, and functional material development

Fig.1 The delivery technologies for oligonucleotides (ONs).1

Why Choose Creative Biolabs?

One-Stop Development CapabilityFrom oligonucleotide modification and conjugation strategy design to purification and characterization, we provide an integrated workflow that helps reduce time loss and quality risk across multiple vendors.
Flexible Chemistry OptionsWe support multiple proven oligonucleotide conjugation chemistries, including click chemistry, thiol-selective conjugation, amide coupling, and enzymatic ligation, with routes tailored to different molecular formats and project goals.
Broad Molecular CompatibilityOur platform supports siRNA, ASOs, DNA, RNA, aptamers, peptides, small molecules, polymers, nanoparticles, and particulate carriers across a broad range of project types.
Orthogonal Analytical VerificationWe apply LC-MS, HPLC, CE, UV-Vis, DLS, or related techniques to ensure each conjugate is verifiable, traceable, and suitable for downstream use.
Application-Oriented CustomizationWe focus not only on successful conjugation, but also on whether the final construct truly improves delivery, targeting, detection, or imaging performance in line with the client’s research objective.

What Our Clients Say

“Creative Biolabs helped us rapidly optimize a peptide-siRNA conjugation route with solid purity and reproducibility. Their analytical feedback was especially valuable during our early screening stage.”

— Dr. Wilson Biotechnology Company in Boston

“We were looking for a partner capable of handling both oligonucleotide modification and nanoparticle conjugation. The team delivered a well-characterized construct package that supported our downstream validation smoothly.”

— Prof. Chen Research Institute in Singapore

“Their scientists provided practical guidance on linker selection and purification strategy for a folate-oligonucleotide project. The communication was efficient and technically grounded.”

— Dr. Martinez Oncology R&D Team, California

Frequently Asked Questions

Reference

Hammond, Suzan M., et al. "Delivery of oligonucleotide‐based therapeutics: challenges and opportunities." EMBO molecular medicine 13.4 (2021): e13243. Distributed under Open Access license CC BY 4.0.

For research use only. Not intended for any clinical use.