Creative Biolabs develops custom aptamer-oligonucleotide conjugates for researchers who need cell-selective delivery of siRNA, antisense oligonucleotides, miRNA modulators, splice-switching oligos, immune-active oligonucleotides, or other research nucleic acids. We support architecture design, oligonucleotide chemistry, conjugation or chimera assembly, purification, structural and binding characterization, cellular uptake, and payload-specific functional validation.
Discuss Your ApOC Development ProjectOur Aptamer-Oligonucleotide Conjugate (ApOC) Development Service creates bifunctional constructs in which an aptamer provides target recognition and an attached oligonucleotide provides the intended regulatory, silencing, splice-modulating, or immune activity. The service is suitable for target-positive cell delivery studies, receptor-mediated internalization research, gene knockdown, transcript correction, pathway interrogation, and early proof-of-concept programs that require a defined molecular conjugate rather than a conventional carrier.
Projects can begin with a customer-supplied aptamer and payload, an existing sequence requiring redesign, or an integrated discovery program. If the targeting ligand is not yet established, we can connect the work with our aptamer development service or one-stop aptamer in vitro selection service. We translate target biology, internalization requirements, payload mechanism, intracellular processing, chemical stability, and assay endpoints into a practical ApOC development plan.
An ApOC design begins with the action the payload must perform after target binding and internalization. Sequence length, strandedness, intracellular destination, processing requirements, and chemical modifications are reviewed together so the targeting and effector domains remain compatible.
We can design aptamer-siRNA chimeras, annealed duplex formats, or linked constructs intended to support target-selective uptake and RNAi. Strand orientation, guide accessibility, overhangs, Dicer processing, and relevant controls are incorporated into the plan.
ASO payloads may be designed for RNase H-dependent transcript reduction, steric blocking, or other sequence-specific mechanisms. Architecture decisions consider target-site accessibility, gapmer or fully modified formats, nuclease stability, and compatibility with aptamer folding.
Aptamer-directed constructs can be explored for delivery of miRNA mimics or inhibitory anti-miRs. We help define strand format, stabilization strategy, reporter or endogenous readout, and target-positive versus target-negative comparisons.
For exon inclusion, exclusion, or splice-site redirection studies, the program can combine a receptor-binding aptamer with a steric-blocking payload and evaluate transcript isoforms using fit-for-purpose RT-PCR or quantitative assays.
CpG-containing or other immune-active oligonucleotides can be incorporated for cell-selective stimulation or pathway studies. Sequence context, receptor compartment, cytokine endpoints, species relevance, and innate immune controls are reviewed before testing.
Other functional DNA or RNA payloads can be considered when their mechanism, synthesis, analytical detection, and intended intracellular action are defined. A feasibility review determines whether direct conjugation, hybridization, or a carrier-assisted alternative is more appropriate.
Sequence discovery, affinity maturation, and target-binding assessment can be coordinated before ApOC assembly.
An ApOC must retain the three-dimensional aptamer fold while keeping the payload accessible to its intracellular machinery. We evaluate the construct as one molecule and use the simplest architecture that can satisfy binding, stability, processing, and activity requirements. Terminal handles and stabilization options can be prepared through our aptamer modification services.
| Design Variable | Options We Can Evaluate | Key Development Question | Representative Evidence |
|---|---|---|---|
| Construct format | Single-chain chimera, annealed duplex, covalent conjugate, hybridization assembly, or modular multi-part format | Which format protects both domains and enables the payload mechanism? | Assembly, purity, integrity, and functional comparison |
| Attachment site | 5′ or 3′ aptamer terminus, payload terminus, internal handle, or sequence extension | Does placement avoid the aptamer binding motif and payload-active region? | Free-versus-conjugated binding and payload activity |
| Spacer or linker | C3/C6 spacers, PEG units, nucleotide extensions, disulfide or other cleavable linkers | Is separation or intracellular release required? | Binding, stability, cleavage, and uptake readouts |
| Conjugation route | Phosphoramidite-based synthesis, thiol-maleimide, azide-alkyne click, amide coupling, or affinity-guided assembly | Is the chemistry selective, scalable, and compatible with both oligos? | Reaction conversion, mass confirmation, and residual free material |
| Chemical stabilization | Selected 2′-F, 2′-OMe, phosphorothioate, terminal capping, or other project-compatible modifications | Can exposure stability improve without impairing folding or RISC/RNase H activity? | Nuclease/serum stability and retained biological function |
| Intracellular processing | Dicer-compatible stem, reducible release, strand displacement, or non-cleavable design | How will the active oligo become available in the relevant compartment? | Processing evidence, knockdown, splice, or reporter response |
We can compare molecular ApOC requirements with aptamer-nanocarrier or direct drug-conjugate strategies.
The workflow is configured around the maturity of your starting materials. Decision points are set before synthesis so non-performing architectures can be revised early and promising constructs can advance with the controls needed for interpretation.
Review target expression, aptamer evidence, payload mechanism, cell model, controls, modifications, and success criteria.
Prepare component oligos and construct selected chimera, duplex, linker, or modular ApOC formats.
Remove free components and side products, confirm identity, assess purity, and verify assembly or conjugation.
Examine integrity, stability, folding or binding retention, and relevant processing or release behavior.
Measure selective association or uptake and the payload-specific molecular or cellular endpoint.
A positive biological result is more useful when the material entering the assay is defined. The analytical package is selected for the construct format and can be coordinated with our broader aptamer characterization services and aptamer in vitro analysis services.
Mass-based confirmation, chromatography or electrophoresis, strand stoichiometry, and residual free aptamer or payload as appropriate.
Duplex formation, thermal behavior, secondary-structure review, and integrity under handling or assay conditions.
Time-course integrity in selected serum, biological matrix, or nuclease challenge conditions with formulation-relevant comparators.
Fit-for-purpose evaluation of Dicer processing, linker cleavage, strand liberation, or another activation step when required by the design.
Conjugation can change aptamer folding, steric access, charge distribution, and apparent affinity. We therefore select a binding format suited to the target and compare the finished ApOC with the unconjugated aptamer whenever possible.
Assay choice depends on target type, available reagents, fluorophore placement, expected receptor abundance, and the question the study must answer.
ELONA and other binding formats can be integrated when they suit the target and construct.
Functional studies are built to distinguish aptamer-dependent delivery from nonspecific oligonucleotide exposure. Depending on the payload, endpoints may include transcript knockdown by RT-qPCR, protein reduction by immunoassay or western blot, splice-isoform change, reporter modulation, downstream pathway response, cytokine release, cell phenotype, or another project-defined readout.
Recommended comparisons may include free aptamer, free payload, unconjugated mixture, non-targeting or scrambled payload, binding-deficient construct, target-negative cells, competition conditions, and a benchmark transfection reagent. Where complement biology is central to the target or endpoint, the project can also connect with our complement component inhibitor development service.
A staged design can begin with binding and uptake, proceed to molecular activity, and add phenotype only after the upstream steps are supported. This approach helps identify whether a weak result originates from targeting, internalization, endosomal access, payload processing, or sequence activity.
Share your target, aptamer, payload, and desired endpoint for a project-specific study design.
These original studies illustrate direct aptamer-siRNA chimera design, target-cell recognition, intracellular gene silencing, and the relationship between molecular conjugates and carrier-assisted delivery systems.
Zeng and colleagues connected a PD-L1 aptamer with CD47 siRNA through an internal spacer and evaluated binding, uptake, gene silencing, immune-cell effects, and antitumor activity.
View research via DOI
Chen and colleagues developed an OX40 aptamer-PD-1 siRNA chimera, examined target-cell binding and silencing, and incorporated the construct into a gold nanoparticle-collagen platform.
View research via DOI
Salve and colleagues linked a MUC1 aptamer to a PEGylated dendritic system, then assessed siRNA loading, target-cell uptake, survivin knockdown, and downstream apoptosis.
View research via DOIYes. We can review the aptamer sequence, target-binding and internalization evidence, payload sequence and mechanism, terminal modifications, available analytical data, and preferred cell model. The review identifies whether the proposed components can be used directly or whether sequence, chemistry, or architecture optimization should come first.
Programs may involve siRNA or Dicer-substrate RNA, antisense oligonucleotides, miRNA mimics, anti-miRs, splice-switching oligos, immune-active oligonucleotides, and other research DNA or RNA payloads. Feasibility depends on payload mechanism, sequence format, chemistry, synthesis, analytical detection, and the intracellular compartment in which it must act.
The choice is based on aptamer folding, payload strandedness, attachment-site tolerance, required intracellular processing, stability, synthesis route, and assay objectives. Direct chimeras can provide a compact defined sequence, while duplex or linker-based designs may offer more flexibility for strand assembly, separation, or release.
Selected 2′-F, 2′-OMe, phosphorothioate, terminal caps, spacers, or other project-compatible modifications can be considered. Modifications are placed with attention to aptamer folding and the payload's mechanism because excessive or poorly positioned stabilization can reduce target binding, Dicer processing, RISC loading, RNase H activity, or splice modulation.
We use a target-appropriate binding assay and, where feasible, compare the completed ApOC with the free aptamer. Target-positive and target-negative models, concentration-response analysis, competition or blocking conditions, and binding-deficient controls can help distinguish retained target recognition from nonspecific association.
The readout is selected for the payload mechanism. Examples include transcript knockdown, protein reduction, splice-isoform change, miRNA reporter response, cytokine release, pathway modulation, or another defined phenotype. Free payload, scrambled or non-targeting payload, unconjugated mixture, and benchmark transfection controls can be included when appropriate.
Helpful inputs include the biological target, aptamer sequence and modifications, binding and internalization data, payload sequence and intended mechanism, preferred architecture, cell or tissue model, required controls, sample quantity, analytical expectations, and the decision the final dataset should support. If some information is unavailable, we can begin with a focused feasibility assessment.
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