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Oligonucleotide Conjugation & Biomolecule Bioconjugation Services

High-loading, low-background oligonucleotide conjugates — including antibody–oligonucleotide conjugates, GalNAc–oligonucleotide conjugates, peptide–siRNA, aptamer–drug, antibody–PNA, and oligonucleotide–protein formats — engineered with full analytics and documentation by Bio-Synthesis.

Speak to a Scientist Overview Antibody & Protein–Oligo
45+ Years of Oligo Experience
ISO 9001:2015 / ISO 13485:2016
Custom & OEM / Kit Support
Texas, USA
Overview Antibody & Protein–Oligo Ligand-Targeted Oligos Aptamer & Small-Molecule Nanoparticle & Surface Lipid & Polymer Oligos Speak to a Scientist

oligo bioconjugation Overview

High-loading, low-background oligonucleotide bioconjugates—spanning antibody– siRNA, GalNAc–siRNA, peptide–siRNA, aptamer–drug, antibody–PNA, and oligonucleotide–protein formats—are engineered with full analytics and documentation by Bio-Synthesis. Oligonucleotide bioconjugation enables the linkage of siRNA, ASO, DNA, RNA, PNA, and aptamers to antibodies, proteins, peptides, ligands, nanoparticles, lipids, polymers, and surfaces to create targeted therapeutics, delivery systems, diagnostics, and imaging agents.

Our oligonucleotide conjugation services cover design, synthesis, and bioconjugation of custom oligonucleotide conjugates for discovery, preclinical, and diagnostic applications.

Bio-Synthesis provides end-to-end oligo bioconjugation services; from oligo synthesis and modification through conjugation, purification, analytics, and full documentation—supporting both discovery and OEM/kit applications. Our platform is optimized for high functional loading, minimal non-specific binding, and tight lot-to-lot reproducibility.

Biomolecule Carrier
Antibody · Protein · Peptide · Ligand
Conjugation Chemistry
NHS · Maleimide · Click · Enzymatic
Oligonucleotide Payload
siRNA · ASO · DNA/RNA · PNA · Aptamer
Therapeutic & Delivery Conjugates

Antibody–siRNA, GalNAc–siRNA, peptide–siRNA, lipid–oligo, and polymer–oligo designs for in vivo delivery and targeted knockdown.

Diagnostic & Imaging

Aptamer–drug probes, fluor/quencher oligos, HRP/AP conjugates, microarrays, and chip or bead capture reagents.

Documentation & Scale

Method summaries, CoAs, and optional tech transfer to support preclinical, kit, or OEM programs.

Oligonucleotide Bioconjugation Services
  • Oligonucleotide-Peptide Conjugates (siRNA-peptide, ASO-peptide, PNA-peptide, Morpholino-peptide, Aptamer-peptide conjugates.
  • Oligonucleotide–Protein / Oligonucleotide–Antibody Conjugates for targeting, capture, and reporter formats.
  • Oligonucleotide–Drug Conjugates (PDCs) for oncology, anti-infective, immunomodulatory, and theranostic use.
  • Oligonucleotide–Polymer & Biomaterial Conjugates including PEG, hydrogels, and scaffolded peptide displays.
  • Oligonucleotide–Nanoparticle Conjugates (gold, magnetic, polymeric, silica, and other nanocarriers).
  • Oligonucleotide–Lipid Conjugates for membrane anchoring, self-assembly, and lipid-based delivery systems.
  • Oligonucleotide–Carbohydrate / Ligand Conjugates for glycan targeting, receptor binding, and multivalent display.
  • Oligonucleotide–Fluorophore & Imaging Conjugates using visible, NIR, and specialty imaging dyes or chelators.
  • Oligonucleotide–Surface & Solid-Support Conjugates on beads, plates, chips, and biosensor surfaces.
  • Oligonucleotide–Chemical Handle / Click-Ready Conjugates (azide, alkyne, tetrazine, DBCO, thiol, and more).
  • Oligonucleotide Therapeutic Conjugates integrating peptides with drugs, biologics, or carriers for therapy.
  • Oligonucleotide Diagnostic & Biosensor Conjugates tailored for in vitro diagnostics, point-of-care, and biosensing.

Oligo bioconjugation can also be combined with carrier delivery systems (ADC & LNP) and broader bioconjugation services from Bio-Synthesis.

Antibody–Oligonucleotide Conjugates

Antibody and protein–oligonucleotide conjugates combine the specificity of biologics with the programmability of nucleic acids to enable targeted delivery, controlled knockdown, and multiplexed detection formats. Bio-Synthesis designs and manufactures custom antibody–siRNA, antibody–ASO, protein–DNA/RNA, and PNA-based conjugates using optimized chemistries and spacers, delivering high-loading, low-aggregation constructs with verified binding, defined conjugation ratios, and full analytical documentation.

Antibody / Protein Carrier
mAb · Fab · scFv · Enzyme
Conjugation Chemistry
NHS · Maleimide · Click · Enzymatic
Oligonucleotide Payload
siRNA · ASO · DNA/RNA · PNA
Product Highlights
  • Antibody–siRNA and antibody–ASO formats for receptor-targeted gene silencing.
  • Antibody–PNA and protein–PNA constructs for high-affinity hybridization and labeling.
  • Full-length mAb, Fab/scFv, nanobody, and enzyme–oligo conjugation options.
  • Defined conjugation ratios, optional site-selective strategies, and aggregation control.
Preferred Applications
  • Targeted delivery of siRNA/ASO to tumor or immune cells via antibody recognition.
  • Oligo-tagged antibodies for multiplexed imaging or barcoded readouts.
  • Enzyme–oligo fusion reagents for signal amplification and proximity assays.
  • Proof-of-concept and optimization campaigns for oligo–antibody therapeutics.

Conjugation Strategy
  • Match oligo handle (amine, thiol, azide, alkyne) to antibody/protein surface chemistry.
  • Minimize impact on Fc or binding sites by favoring controlled or site-selective approaches.
  • Use PEG/spacer arms to reduce steric clash and maintain antigen binding.
  • Monitor conjugation ratio and aggregation by intact MS and SEC-HPLC.
Formulation & Stability
  • Align buffer composition with both oligo and antibody stability windows.
  • Include stress testing (freeze–thaw, agitation, temperature) where needed.
  • Check functionality via antigen binding and oligo hybridization or activity assays.
  • Define acceptance criteria around binding, conjugation ratio, and purity.

Example of an IgG antibody–siRNA conjugation study. Multiple conjugation ratios and spacer lengths were tested to balance binding affinity, siRNA loading, and internalization efficiency.

  • Controlled conjugation ratios confirmed by UV/MS and SEC.
  • Binding preserved across all conjugates (>90% of parental mAb).
  • Knockdown assessed via qPCR and protein-level readouts in relevant cell models.
IgG Antibody Conjugates
  • siRNA: MW 14,609.60
  • IgG protein: ~150 kDa
  • Targeting a clean 1:1 IgG:siRNA conjugation ratio
IgG–siRNA Purification
IgG–siRNA purification chromatogram
Figure 1. IgG–siRNA conjugate purification profile (example image).
IgG–siRNA UV spectrum
Figure 2. UV spectrum of IgG–siRNA fractions.
IgG–siRNA UV spectrum repeat
Figure 3. Additional UV trace confirming conjugate purity.
IgG–siRNA SDS-PAGE gel analysis
Figure 4. SDS-PAGE analysis showing IgG–siRNA 1:1 vs 1:2 conjugation species.
Conclusion
  • Purification is essential to isolate a clean 1:1 IgG:siRNA conjugate.
  • Overall conjugation yield for 1:1 and 1:2 IgG:siRNA species is typically <10%.
  • Chromatography allows separation of 1:1 from 1:2 species with high confidence.

Oligo
Sequence, chemistry (siRNA, ASO, DNA/RNA, PNA), handles (e.g., 5′-amine, 3′-thiol), and purity.
Carrier
Antibody/protein identity, format (mAb, Fab, scFv, enzyme), concentration, and buffer.
Goals
Target conjugation ratio, preferred chemistry, and functional tests (binding, knockdown, etc.).
Specs
Lot size, stability expectations, and any documentation required for kit or preclinical use.

Ligand-Targeted Oligonucleotide Conjugates (GalNAc, Peptides & More)

Ligand-targeted oligonucleotide conjugates use small, well-defined targeting motifs—such as GalNAc, peptides, folate, or RGD—to direct siRNA, ASO, or other oligos to specific tissues and receptors. Bio-Synthesis develops custom GalNAc–oligo, peptide–oligo, and other ligand–oligo formats with tuned valency, spacer length, and conjugation chemistry to support potent, receptor-driven delivery, providing route scouting, scale-up, and QC packages suitable for discovery, preclinical, or diagnostic work.

Targeting Ligand
GalNAc · Peptide · Folate · RGD
Conjugation Chemistry
Amide · Click · Spacer/PEG
Oligonucleotide Payload
siRNA · ASO · DNA/RNA
Product Highlights
  • GalNAc–siRNA and GalNAc–ASO for hepatocyte-targeted oligo therapeutics.
  • Peptide–siRNA and peptide–oligo conjugates (CPPs, tumor-targeting, NLS, endosomal escape).
  • Folate-, RGD-, and other ligand–oligo conjugates for receptor-directed delivery.
  • Spacer- and valency-optimized architectures for potency and safety profiles.
Preferred Applications
  • Liver-targeted siRNA/ASO programs using GalNAc structures.
  • Peptide-directed delivery to specific tissues, tumors, or intracellular compartments.
  • Receptor-ligand-based targeting for research and therapeutic candidates.
  • Structure–activity relationship (SAR) campaigns for ligand density and spacing.

Ligand & Oligo Design
  • Define ligand valency (mono-, tri-, tetra-antennary for GalNAc and other ligands).
  • Control linker length and branching to balance targeting and pharmacokinetics.
  • Align oligo modifications (e.g., phosphorothioate, 2′-OMe, 2′-F) with target biology.
  • Review receptor expression, species cross-reactivity, and dosing route.
Assay & QC Considerations
  • Confirm conjugation and valency by LC-MS and analytical HPLC/UPLC.
  • Use in vitro potency assays (e.g., mRNA knockdown) to benchmark designs.
  • Include stability studies in serum or relevant matrices.
  • Monitor aggregation or self-assembly where ligands are hydrophobic or multivalent.

A series of GalNAc–siRNA conjugates were synthesized with differing valency and spacer lengths to modulate hepatocyte uptake. Potency and duration of knockdown were measured in relevant in vitro and in vivo systems.

  • Tri- vs tetra-antennary GalNAc architectures compared head-to-head.
  • Optimization of spacer length to minimize off-target accumulation.
  • Confirmation of liver-selective distribution via biodistribution studies.
siRNA-TriGalNac Conjugates
  • Sense strand of siRNA MW: 8908.58950
  • Targeting siRNA conjugated Oligo with >95% pure
ESI, HPLC, Duplex Analaysis
Maleimide Conjugation Chemistry
Figure 1. Sense strand of siRNA conjugation to TriGalNAc

Peptide-siRNA conjugates were synthesized with differing valency and spacer lengths to modulate hepatocyte uptake. Potency and duration of knockdown were measured in relevant in vitro and in vivo systems.

  • Tri- vs tetra-antennary GalNAc architectures compared head-to-head.
  • Optimization of spacer length to minimize off-target accumulation.
  • Confirmation of liver-selective distribution via biodistribution studies.
Peptide-siRNA Conjugates
  • Peptide: MW 1100.33
  • Sense strand of siRNA MW: 6696.49
  • Targeting with Sense Strand Conjugates MW: 8112.17
Final Construct
Maleimide Conjugation Chemistry
Figure 1. Sense strand of siRNA conjugation to peptide
Analytical HPLC and Mass Spec Result
Figure 1. Sense strand of siRNA conjugation to peptide

Oligo
Sequence, modifications, intended target, and required potency metrics if available.
Ligand
GalNAc, peptide, folate, RGD, or other ligand identity, target receptor, and structure.
Design Goals
Valency, spacer design, and therapeutic vs research use case.
Assays
In vitro potency, uptake, or receptor competition assays you plan to run.

Aptamer & Small-Molecule Oligonucleotide Conjugates

Aptamers are short, single-stranded DNA or RNA oligonucleotides that fold into precise 3D structures, enabling high-affinity, specific binding to proteins, peptides, small molecules, or cells with antibody-like performance. Bio-Synthesis leverages these properties to create custom Aptamer–Drug Conjugates (ApDCs), coupling aptamers to cytotoxic agents, imaging probes, or functional small molecules using optimized linkers and chemistries. These tailored conjugates support targeted delivery, reduced off-target toxicity, and enhanced local drug concentration, with full service coverage from aptamer modification and design through conjugation, purification, and QC characterization.

Aptamer / Small Molecule
Aptamer · Drug · Fluorophore
Conjugation Chemistry
Click · Amide · Cleavable
Oligonucleotide Scaffold
DNA/RNA · Aptamer · Beacon
Product Highlights
  • Aptamer–drug conjugates (ApDCs) for targeted delivery and controlled release.
  • Aptamer–probe conjugates for binding, imaging, and biosensor applications.
  • Oligo–small molecule conjugation (e.g., toxins, inhibitors, labels).
  • Covalent and cleavable linkers tailored to your therapeutic or diagnostic goals.
Preferred Applications
  • Targeted cytotoxic delivery using aptamer–drug conjugates.
  • Labeling and tracking of aptamer binding in cells or in vivo.
  • Small-molecule–oligo conjugates for affinity capture or screening.
  • Biosensor and microarray platforms using aptamer-based recognition.

Aptamer ligands can also be displayed on liposomes or LNP-style carriers; see
Lipid & Polymer Oligonucleotide Conjugates for targeted liposomal systems.

Aptamer Considerations
  • Preserve aptamer folding and binding by placing conjugation sites away from critical motifs.
  • Assess impact of conjugation on Kd and on-target binding versus parent aptamer.
  • Use PEG or spacers to distance bulky drugs or labels from the binding interface.
Drug & Label Handling
  • Select linkers compatible with drug stability and release requirements.
  • Consider photocleavable, enzymatic, or pH-sensitive linkers where controlled release is needed.
  • Confirm drug:oligo stoichiometry and batch homogeneity by LC-MS.

A tumor-targeting aptamer was conjugated to a small-molecule cytotoxic agent via a cleavable linker, producing an aptamer–drug conjugate evaluated in cell-based and in vivo models.

  • Binding maintained versus parent aptamer while carrying a drug payload.
  • Enhanced cell kill observed in target-positive versus target-negative cells.
  • Linker design tuned to balance stability and intracellular release.
Peptide-siRNA Conjugates
  • Conjugated MW: 8396.55
  • MALDI-TOF MS: 8397.14
  • Targeting Purity: >90%
Taxol Oligo Conjugation
Figure 1. Conjugation of Taxol to 5' end of Aptamer

Aptamer / Oligo
sequence, secondary structure or motif information, and known Kd if available.
Small Molecule
Identity, stability profile, and any existing conjugation handles.
Linker Requirements
Cleavable vs non-cleavable, release mechanism, and acceptable off-target profile.
Assay Plans
Binding, internalization, cytotoxicity, or sensor readouts to be used for evaluation.

Nanoparticle & Surface Oligonucleotide Conjugates

Nanoparticle and surface–oligonucleotide conjugates harness gold particles, magnetic beads, plates, chips, and other solid supports to present capture, probe, or reporter oligos in a controlled, assay-ready format. Bio-Synthesis prepares custom oligo–gold, oligo–bead, and surface-immobilized oligo reagents with tuned surface density, blocking, and coating conditions, supporting applications such as lateral flow, SPR/BLI, NGS workflows, and microarrays with lot-controlled manufacturing and functional QC.

Nanoparticle / Surface
Gold NP · Beads · Chips
Conjugation Chemistry
Thiol–Gold · Biotin–Streptavidin · Click
Oligonucleotide Payload
Capture · Probe · Reporter
Product Highlights
  • Gold nanoparticle–oligo conjugates for lateral flow and plasmonic assays.
  • Magnetic bead–oligo conjugates for capture, enrichment, and NGS workflows.
  • Chip and sensor surface–oligo functionalization for SPR/BLI and biosensors.
  • Custom surface density, blocking, and lot-controlled manufacturing.
Preferred Applications
  • Lateral flow and point-of-care diagnostics using oligo–gold conjugates.
  • Magnetic bead capture for NGS library prep, depletion, and enrichment.
  • Oligo-functionalized sensor surfaces for label-free binding measurements.
  • Microarray and imaging platforms with high-density oligo probes.

Surface Chemistry & Coating
  • Use thiol–gold and biotin–streptavidin chemistries for well-established platforms.
  • Control oligo density to avoid steric crowding and maintain hybridization performance.
  • Select PEG or mixed self-assembled monolayers to reduce non-specific binding.
QC & Performance
  • Characterize size distribution and aggregation for nanoparticle conjugates.
  • Evaluate signal-to-background ratio in relevant assay buffers and matrices.
  • Assess lot-to-lot reproducibility with standardized functional tests.

A set of gold nanoparticle–oligo conjugates were prepared for use in a lateral flow assay designed to detect a specific nucleic acid target. Conjugation conditions and blocking strategies were optimized to maximize signal and minimize background.

  • Particle size and absorbance verified post-conjugation.
  • Hybridization performance confirmed across assay temperature and buffer conditions.
  • Demonstrated improved sensitivity compared to a non-conjugated control format.

Oligo
Sequence, role (capture/probe/reporter), and required melting temperature or design constraints.
Nanoparticle / Surface
Gold NP, magnetic bead, plate, chip, or resin type, vendor specs, and size or coating details.
Assay Format
Lateral flow, microarray, SPR/BLI, NGS, or other assay type, including detection method.
Specifications
Desired coating density, background thresholds, lot size, and stability targets.

Lipid & Polymer Oligonucleotide Conjugates

Lipid and polymer–oligonucleotide conjugates integrate hydrophobic or polymeric carriers—such as cholesterol, lipid tails, PEG, and PLGA—with siRNA, ASO, or DNA/RNA to improve exposure, uptake, and formulation compatibility. Bio-Synthesis designs and produces custom lipidated and polymer–oligo constructs, optimizing attachment position, linker and PEG architecture, and chemistry to align with your LNP, micelle, or nanoparticle systems, and provides supporting analytics, stability assessments, and documentation for in vivo and formulation-focused programs.

Lipid / Polymer Carrier
Cholesterol · PEG · PLGA
Conjugation Chemistry
Amide · Click · Hydrophobic Tail
Oligonucleotide Payload
siRNA · ASO · DNA/RNA
Product Highlights
  • Cholesterol–siRNA and Chol–ASO conjugates for improved circulation and uptake.
  • Lipid-tail–siRNA and lipid–oligo conjugates for formulation into LNPs or micelles.
  • Polymer–oligo conjugates (e.g., PEG, PLGA, dendrimers) for delivery and controlled release.
  • Aptamer–liposome conjugates for targeted liposomal delivery and enhanced cellular uptake.
  • Custom architectures supporting combination with carrier delivery platforms.
Preferred Applications
  • In vivo-ready oligonucleotide conjugates designed for systemic administration.
  • Lipidated oligos for inclusion into LNP or lipid-based delivery systems.
  • Polymer–oligo constructs for depot, slow-release, or targeted formulations.
  • Targeted liposomal delivery using aptamer-decorated liposomes for receptor-specific uptake.
  • Bridging between small-scale discovery and scalable formulation platforms.

Lipid/Oligo Design
  • Select lipid moieties aligned with your target organ and formulation system.
  • Control position of attachment (5′ vs 3′) and backbone chemistry to maintain potency.
  • Consider linker and PEG length to tune solubility and aggregation behavior.
Formulation Interface
  • Align conjugation strategy with intended carrier (LNP, micelle, polymer nanoparticle).
  • Assess physicochemical properties (logP, charge, critical micelle behavior) as needed.
  • Include stability and potency testing in target formulation buffers.

A panel of Lipid DCA–Oligonucleotide conjugates was prepared to evaluate sequence- and chemistry-dependent effects on in vivo potency. Multiple backbones and conjugation positions were compared under uniform dosing conditions.

  • Backbone and 5′/3′ conjugation position impacted exposure and activity.
  • Optimized constructs showed improved potency at lower doses.
  • Compatibility with downstream LNP or carrier formulation was evaluated.
Oligonucleotide DCA Lipid Conjugation
  • Conjugated MW: 7520.47846
  • ESI: 7521.0
  • Targeting Purity: >95%
DCA lipid Oligo Conjugates
Figure 1. Lipid DCA Oligonucleotide Conjugation

Oligo
Sequence, chemistry type (siRNA, ASO, DNA/RNA), and existing modifications.
Lipid/Polymer
Cholesterol, lipid tail, PEG, PLGA, dendrimer, or other carrier details.
Formulation Plan
Intended carrier (LNP, micelle, nanoparticle, etc.) and route of administration.
Specifications
Target potency, stability, and any constraints from downstream formulation partners.

Technical Summary — Oligo Bioconjugation Platform

Workflow
  • Project intake and design review (oligo, carrier, application, and risk mapping).
  • Conjugation route scouting and spacer/linker optimization.
  • Scale-up with in-process monitoring and process control.
  • Purification and polishing tailored to the conjugate type.
  • QC and documentation aligned with your downstream needs.
Controls & Comparators
  • Unconjugated oligo and carrier controls.
  • Spacer length, linker type, and conjugation position variants.
  • Cleavable vs non-cleavable conjugate comparisons.
  • Functional benchmarks (potency, binding, assay performance).
Analytics & Documentation
  • Identity and purity by LC-MS and HPLC/UPLC.
  • Conjugation ratio, aggregation, and functional assays as applicable.
  • Certificates of Analysis and optional tech transfer packages.

FAQ

Which oligo types do you support?

We work with siRNA, ASO, DNA, RNA, aptamers, mixmer designs, and PNA/LNA-based structures, including a wide range of 5′ and 3′ modifications suitable for bioconjugation.

Can you both synthesize the oligo and perform the conjugation?

Yes. Bio-Synthesis can synthesize, purify, and QC the oligo, then perform the bioconjugation and provide the final conjugate as a single workflow.

Do you support GMP or diagnostic kit/OEM projects?

We support projects that require enhanced documentation, lot control, and stability programs suitable for regulated or kit/OEM environments. We align release criteria with your internal specifications.

What information do you need to scope a project?

At minimum, we need your oligo sequence/chemistry, carrier identity, intended conjugation type, application, and any required performance metrics (potency, binding, assay readout, or stability).

Can you work under NDA and handle proprietary sequences?

Yes. Bio-Synthesis routinely works under NDA/MSA and treats all sequences, materials, and results as confidential.

How do you manage timelines and communication?

We provide an initial scope and projected timeline based on route complexity, then keep you updated at key milestones (e.g., synthesis, conjugation, QC) and share data packages at completion.

Contact

Speak to an Oligo Bioconjugation Scientist

Share your oligo sequence format, carrier, application, and target performance. We will recommend a conjugation route, linker strategy, and QC package, then provide a project quote.

Request a Quote Feasibility Review OEM / Kit Partner Sample Submission
Email: sales@biosyn.com
Phone: +1-972-420-8505
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Recommended Reading & Bio-Synthesis Resources

  1. Odete Sofia Lopes Goncalves(2019).Royal Socienty of Chemistry Detection of miRNA cancer biomarkers using light activated Molecular Beacons.
  2. Hermanson, G. T. (2013). Bioconjugate Techniques, 3rd Ed. Academic Press — Core reference for oligo–protein, oligo–peptide, and surface bioconjugation chemistries.
  3. Khvorova, A. & Watts, J. K. (2017). Oligonucleotide therapeutics: from chemistry to medicine. Nat. Biotechnol. — Overview of siRNA/ASO chemistries and delivery strategies.
  4. Juliano, R. (2016). The delivery of therapeutic oligonucleotides. Nucleic Acid Ther. — Discussion of conjugated and nanocarrier-based oligo delivery systems.
  5. Bio-Synthesis, Inc. — Application notes, technical bulletins, and white papers on custom oligonucleotide & biomolecule bioconjugation, available from Bio-Synthesis upon request or via the company website.

Why Choose Bio-Synthesis

Trusted by biotech leaders worldwide for over 40+ years of delivering high quality, fast and scalable synthetic biology solutions.

Greetings Researchers,

Please be advised that any information, guidelines, writeups, and oral/video/graphic content on our website are intended solely as general guidelines.
It is the researcher's sole responsibility to conduct thorough research on the designs of the products intended for their experiments before submitting
their designs to Biosynthesis for review of production feasibility.
Thank you for your understanding.

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