Nanobody–oligonucleotide conjugates combine the target-selective recognition of single-domain antibody fragments with programmable DNA or RNA payloads for targeted delivery, receptor-directed gene silencing, molecular imaging, and advanced research workflows.
Nanobody–oligonucleotide conjugates are a specialized class of protein–oligonucleotide conjugates in which a nanobody is linked to an oligonucleotide payload such as siRNA, antisense oligonucleotides (ASO), splice-switching oligonucleotides (SSO), PMO, morpholino, and related RNA therapeutic formats. These constructs combine target-specific recognition with the programmable function of nucleic acid therapeutics and have emerged as promising architectures for targeted RNA delivery, receptor-mediated uptake, and molecular imaging [1].
Because nanobodies are substantially smaller than full-length antibodies (~15 kDa vs ~150 kDa), they can offer improved tissue penetration, simplified recombinant engineering, and more controlled conjugation strategies compared with conventional antibody–oligonucleotide conjugates [2].
In the literature, these constructs are also described as nanobody–siRNA conjugates or nanobody-mediated RNA delivery systems.
We support custom nanobody–oligonucleotide conjugation with project-dependent linker and payload design, including site-specific and bioorthogonal strategies for protein–RNA and protein–DNA conjugate architectures.
Nanobody recognition domains can direct oligonucleotide payloads to defined receptors or cell populations.
Supports siRNA, ASO, SSO, PMO, morpholino, miRNA-related oligos, aptamers, and selected guide-RNA style constructs.
Compatible with maleimide-thiol, click chemistry, NHS coupling, and other controlled protein–oligonucleotide linker strategies.
Representative workflow showing llama immunization, nanobody discovery and purification, followed by construction of the final nanobody–oligonucleotide conjugate for siRNA, ASO, SSO, PMO, and related payload formats.
A nanobody–oligonucleotide conjugate is typically organized as a target-binding nanobody, a defined linker or conjugation handle, and an oligonucleotide payload. The exact architecture depends on whether the project prioritizes receptor targeting, intracellular release, splice modulation, imaging, or analytical detection.
Provides receptor or antigen recognition and determines the biological entry point for the conjugate.
Controls orientation, spacing, cleavability, and the degree of site specificity in the final construct.
Can be siRNA, ASO, SSO, PMO, morpholino, or other nucleic acid formats depending on the intended mechanism.
Nanobodies are attractive targeting domains for oligonucleotide conjugation because they combine high target specificity, compact size, recombinant accessibility, and modular engineering flexibility. In many delivery and imaging workflows, these properties can simplify conjugate architecture while preserving strong target recognition.
Nanobodies are far smaller than full antibodies, which can support better tissue penetration and reduce steric burden in conjugate design.
Recombinant production can simplify engineering of site-specific handles and controlled conjugation positions.
Nanobody binding can bias delivery toward defined receptors, tumor markers, or disease-relevant cell populations.
Nanobodies are single-domain antibody fragments derived from heavy-chain-only antibody systems. Their compact structure is one of the main reasons they are useful in oligonucleotide conjugation, especially when a smaller targeting scaffold is preferred over a full immunoglobulin.
Chemistry choice affects stoichiometry, orientation, activity retention, and manufacturability.
Tumor-associated receptors and antigens can be explored for targeted nanobody–siRNA or nanobody–ASO delivery studies.
Nanobody recognition enables receptor-directed uptake studies and mechanistic investigation of targeted nucleic acid delivery.
Nanobody–oligo architectures can also support molecular imaging, barcoding, and probe-based assay development.
The examples below illustrate common target classes researchers may consider when designing nanobody-mediated oligonucleotide delivery or probe systems.
Both nanobody–oligonucleotide and antibody–oligonucleotide conjugates can provide targeted recognition, but they are not interchangeable. The best choice depends on payload, target biology, desired tissue penetration, and how much control is needed over conjugation architecture.
Broader protein–DNA and protein–RNA conjugation services spanning recombinant proteins, enzymes, antibodies, and carrier proteins.
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Full-antibody oligonucleotide conjugation for detection, barcoding, and targeted delivery applications.
Custom siRNA conjugates with peptides, proteins, targeting ligands, and delivery modifiers.
Antisense oligonucleotide conjugation for targeted research and therapeutic development workflows.
Click-compatible oligonucleotide conjugation strategies for modular and site-specific buildouts.
Custom nanobody-centric conjugation design support across nucleic acid, small-molecule, and imaging-oriented workflows.
Common payloads include siRNA, antisense oligonucleotides (ASO), splice-switching oligonucleotides (SSO), phosphorodiamidate morpholino oligonucleotides (PMO), miRNA-related oligonucleotides, aptamers, and selected guide RNA constructs depending on design goals.
Nanobodies are much smaller than full antibodies, which can improve tissue penetration, simplify recombinant production, and enable more controlled conjugation strategies while preserving target-specific recognition.
Common strategies include maleimide-thiol coupling, NHS-amine coupling, azide-alkyne click chemistry, DBCO-based copper-free click chemistry, and other site-specific linker strategies depending on the nanobody and oligonucleotide design.
These conjugates are used for targeted gene silencing, receptor-directed delivery, molecular imaging, diagnostic research, and precision oncology or cell-targeting studies.
Yes. Nanobodies can be conjugated to siRNA, antisense oligonucleotides (ASO), splice-switching oligonucleotides (SSO), PMO, morpholino payloads, and other nucleic acid constructs when the chemistry and architecture are matched to the project goal.
A nanobody–oligonucleotide conjugate is a construct in which a single-domain antibody fragment is covalently linked to an oligonucleotide payload such as siRNA, ASO, SSO, or PMO for targeted delivery, detection, or research use.
Key design factors include target selection, nanobody orientation, conjugation site, linker chemistry, cleavable versus non-cleavable design, payload modality, stoichiometry, and the desired balance between stability and intracellular function.
They can be used for both. Some designs focus on targeted delivery of therapeutic oligonucleotides, while others are built for imaging, barcoding, receptor-binding studies, analytical assays, or mechanistic research workflows.
For the fastest review, share the nanobody target, payload modality, desired conjugation chemistry, preferred attachment site, stoichiometry goals, and whether the project is intended for targeted delivery, imaging, or assay development.
Common requests include receptor-targeted siRNA delivery, nanobody–ASO research constructs, splice-modulating nanobody–PMO designs, and site-specific protein–oligonucleotide conjugation development.
Key publications discussing nanobody engineering, antibody–oligonucleotide conjugates, and targeted nucleic acid delivery strategies.
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