Aptamer-Modified Oligonucleotides

Engineer high-affinity aptamer ligands and aptamer-conjugated oligos for diagnostics, targeted delivery, and research. From SELEX discovery to stabilization and conjugation (biotin, dyes, PEG, GalNAc, click), we deliver assay-ready materials with full QC.

SELEX Discovery 2′-OMe / 2′-F / LNA / PS Biotin • Dyes • Click Aptamer–siRNA/ASO PEG / Multivalent RUO → GMP-like

Overview

Aptamers are single-stranded DNA/RNA that fold into 3D structures to bind proteins, small molecules, and cells with antibody-like specificity. Bio-Synthesis supports custom aptamer programs end-to-end—library design & SELEX, sequence optimization and truncation, stabilization chemistries (2′-OMe, 2′-F, LNA/BNA, cEt, partial PS), and conjugations (biotin, fluorophores, PEG, GalNAc, peptides/antibodies, click handles).

We manufacture at scales from µmol to multi-gram with HPLC/UPLC purification, LC-MS confirmation, and optional binding/functional assays. Deliverables include documentation/COA and RUO → GMP-like pathways.

Formats
Tubes • Plates • Kitting
Scale
µmol → multi-gram
QC
UPLC/HPLC • LC-MS • Bind
Supply
RUO → GMP-like
What you get with Bio-Synthesis
  • Design/SELEX: library strategy, selection, counter-selection, truncation, and affinity maturation.
  • Stabilization: 2′-OMe/2′-F; LNA/BNA/cEt blocks; partial PS; end-caps; PEGylation.
  • Conjugation: biotin/streptavidin, dyes (FAM/Cy5/ATTO), GalNAc, PEG, click (azide/DBCO/TCO), peptide/antibody.
  • Chimeras: aptamer–siRNA/ASO fusions; multivalent and bispecific designs.
  • Analytics: HPLC/UPLC, LC-MS, optional Kd/EC50 binding assays.

Also searched as: aptamer oligonucleotide, aptamer conjugate, aptamer-siRNA chimera, biotinylated aptamer, fluorescent aptamer, PEGylated aptamer, GalNAc aptamer.

Quick chooser — pick the right aptamer format

Goal Best pick Why / notes
Surface capture Biotinylated aptamer High-affinity SA/biotin interface; plates, beads, and sensor chips.
Fluorescent readout Fluorescent aptamer (± quencher) Direct detection, FRET/turn-on designs, imaging.
Targeted RNAi Aptamer–siRNA/ASO chimera Cell-type binding + payload knockdown; stabilize with 2′-OMe/2′-F/LNA, PS.
In vivo half-life PEGylated aptamer Improves PK/PD; reduces renal clearance and aggregation.
Modular assembly Clickable aptamer (azide/DBCO/TCO) Bioorthogonal attachment to surfaces, particles, or payloads.

Products & Notes

Service / Modification Description Typical use Code
SELEX Campaign (DNA/RNA) Random library (1013–15 diversity); positive/negative selection; sequencing analysis. Discovery of novel binders to proteins, cells, or small molecules. [SELEX]
Truncation & Optimization Minimal binding motif; stem-loop tuning; affinity maturation. Shorter, cheaper, and more stable binders. [Apt-Opt]
Stabilized Library 2′-OMe/2′-F substitutions; LNA/BNA/cEt blocks; partial PS; end-caps. Resistance to nucleases; improved Kd in serum. [Lib-Stab]
Technical Notes
  • Counter-SELEX: include close homologs/surface materials to suppress off-target binders.
  • Early truncation: map minimal motifs before conjugation to reduce sterics and cost.
  • RNA routes: prefer 2′-F pyrimidines + terminal PS; validate Mg2+/Na+ for folding.

Modification Description Typical use Code
5′-Biotin-TEG Biotin via flexible spacer for reduced sterics. ELONA/ELASA, pull-downs, immobilization. [5′-Bio-TEG]
3′-Biotin-TEG Terminal biotin with capture + blocking of 3′ end. Capture with non-extendable end. [3′-Bio-TEG]
Dual-Biotin Biotin at 5′ and internal/3′ for strong anchoring. High-strength immobilization; flow cells. [Apt-2xBio]
Technical Notes
  • Use TEG/short PEG between biotin and the binding domain to preserve Kd.
  • For polymerase exposure, pair with a 3′ terminator (e.g., 3′-inv-dT or 3′-PO4).
  • Dual-biotin improves anchoring on flow cells and high-shear sensors.

Modification Description Typical use Code
5′-FAM / 3′-FAM Green dye labeling; internal options available. Fluorescence detection, imaging. [FAM-Apt]
Cy5 / ATTO 647N Far-red labels for low background. Imaging, flow cytometry, FRET acceptors. [Cy5-Apt]
Dye + Quencher (BHQ) Turn-on probe designs with stem/loop quenching. Real-time binding assays & sensors. [DQ-Apt]
Technical Notes
  • Place dyes on stems/termini away from the binding pocket; add TEG if bulky.
  • For turn-on probes, tune stem length and pick BHQ/Iowa Black to match emission.
  • Re-check Tm and folding after labeling (buffer/ionic strength dependent).

Format Description Typical use Code
Aptamer–siRNA (duplex) Ligand fused to guide/passenger; 2′-OMe/2′-F/LNA + partial PS. Cell-type specific gene silencing. [Apt-siRNA]
Aptamer–ASO (single) Ligand joined to antisense with stabilizing blocks. Targeted ASO delivery and uptake. [Apt-ASO]
Bispecific / Multivalent Two ligands or ligand+payload on one scaffold. Enhanced avidity or dual targeting. [Apt-Multi]
Technical Notes
  • Stabilization balance: use 2′-OMe/2′-F + partial PS; avoid over-LNA near RISC/target motifs.
  • Junction design: add short PEG/TEG spacers to reduce steric clash.
  • Confirm uptake and knockdown in the final buffer/matrix; include scrambled/non-binding controls.

Format Description Typical use Code
Non-cleavable linker Stable attachment for durable binding or blocking. Receptor antagonism, imaging probes. [Apt-Drug-NC]
Cleavable (disulfide) Reductive release in cytosol (GSH). Intracellular drug delivery. [Apt-Drug-SS]
Cleavable (hydrazone) Acid-labile release (endosomal). Endosomal release strategies. [Apt-Drug-HZ]
Technical Notes
  • Pick cleavable linkers (SS/hydrazone) for intracellular release; non-cleavable for blocking/imaging.
  • Tune linker length/hydrophilicity (PEG) to maintain folding and binding.
  • Site-map attachments away from the pocket; verify Kd post-conjugation.

Modification Description Typical use Code
5′-Azide / 3′-Azide CuAAC/SPAAC-ready handles. Surface coupling, modular probe building. [N3-Apt]
DBCO (SPAAC) Copper-free click partner to azide. Live-cell compatible conjugations. [DBCO-Apt]
TCO IEDDA partner to tetrazine for ultrafast ligation. Rapid labeling; particle assembly. [TCO-Apt]
Technical Notes
  • Insert internal spacers near handles to preserve structure.
  • For CuAAC, ensure nuclease compatibility; prefer SPAAC/IEDDA for live cells.
  • Re-test folding/binding after the click step (salt and solvent history matter).

Format Description Typical use Code
PEGylated (various MW) Linear/branched PEG at 5′/3′ or internal. PK/PD improvement; reduced aggregation. [Apt-PEG]
Multimer (dimer/trimer) Two or more aptamer units on scaffold. Avidity enhancement; multi-epitope binding. [Apt-MultiVal]
Technical Notes
  • Select PEG MW to balance solubility vs. epitope access; avoid masking the pocket.
  • For dimers, match spacer length to receptor spacing to maximize avidity.
  • Confirm activity across relevant shear/flow if used on sensors or particles.

Modification Description Typical use Code
L-DNA (mirror-image) Enantiomer of D-DNA; nuclease-proof; requires mirror-selection strategy (Spiegelmer concept). Extreme serum stability; resistant matrices. [L-DNA]
L-RNA (mirror-image) L-configured ribonucleotides; highly nuclease-resistant; specialized selection routes. In vivo aptamers with extended half-life. [L-RNA]
LNA / BNA Locked ribose (C3′-endo bias) increases Tm and nuclease resistance. Truncation with Kd retention; serum stability. [LNA]
2′-Fluoro (2′-F) 2′-F pyrimidines (± purines) stabilize C3′-endo; strong nuclease resistance for RNA aptamers. RNA aptamers in serum/cell assays. [2F]
2′-O-Methyl (2′-OMe) Bulky 2′-O-Me increases stability; can improve folding robustness. Serum stability with minimal structural perturbation. [2OMe]
2′-O-Methoxyethyl (2′-MOE) Hydrophilic 2′-O substituent; strong nuclease resistance and improved PK. Therapeutic-leaning designs; reduced nonspecific binding. [2MOE]
Partial PS backbone Phosphorothioate at termini/selected positions slows exonuclease attack. Terminal protection; in vivo exposure. [PS]
Technical Notes
  • L-DNA/L-RNA: require mirror-selection strategies; deliver exceptional nuclease resistance.
  • LNA/BNA: place in stems/non-critical regions; over-locking loops can reduce affinity.
  • 2′-F vs 2′-OMe vs 2′-MOE: 2′-F = compact/high stability; 2′-OMe = balanced; 2′-MOE = PK & low nonspecific binding.
  • Combinatorial: mix 2′-F/2′-OMe with LNA blocks + terminal PS; re-validate folding and Kd.

Item Description Typical use Code
Scrambled Aptamer Sequence-shuffled control preserving base composition. Specificity control in binding assays. [Apt-Scr]
Non-binding Mutant Point mutations to disrupt binding loop. Negative control for signal attribution. [Apt-NB]
Positive Control Aptamer Validated binder for benchmark target. Platform qualification, calibration. [Apt-PC]
Services at a glance
  • SELEX & sequence optimization
  • RUO → GMP-like manufacturing
  • QC: UPLC/HPLC, LC-MS, binding assays
Need help picking an aptamer format?

We’ll recommend stabilization, linker strategy, and labels to meet your Kd and assay goals.

Technology • Design • Application

Technology
  • Folding & binding: stem-loops and bulges create pockets for high-affinity recognition.
  • Stabilization: 2′-OMe/2′-F, LNA/BNA/cEt blocks, end-caps, partial PS; PEGylation for PK.
  • Conjugation: biotin/SA, dyes/quencher pairs, click handles, GalNAc, peptides/antibodies.
Design
  • Map labels/linkers away from the binding pocket; add TEG/PEG spacers to limit sterics.
  • For chimeras, keep junction flexible and protect the payload with 2′-mods + PS.
  • Validate folding (CD/fluorescence) and binding (SPR/ELONA/flow) post-modification.
Application
  • Diagnostics: ELONA/ELASA, lateral flow, electrochemical/optical sensors, imaging.
  • Therapeutics: targeted delivery (aptamer–siRNA/ASO), aptamer–drug conjugates.
  • Research: affinity capture, receptor mapping, live-cell labeling without antibodies.

Tip: include scrambled/non-binding controls to track specificity drift across lots and buffers.

FAQ

Do you run SELEX or only synthesize provided sequences?

We offer both. We can execute end-to-end SELEX campaigns or synthesize and optimize your provided aptamer sequences (including truncation and conjugations).

How do you improve serum stability?

Introduce 2′-OMe/2′-F substitutions, LNA/BNA/cEt blocks, partial PS backbones, and consider PEGylation/end-caps. We tune placement to retain binding while resisting nucleases.

What QC data are provided?

Standard packages include HPLC/UPLC traces and LC-MS confirmation; optional binding/functional data (e.g., Kd by SPR/ELONA) are available.

Which labels and linkers do you support?

Biotin, dyes (FAM/Cy3/Cy5/ATTO), quenchers (BHQ/Iowa Black), PEG (various MW), GalNAc, peptide/antibody, and bioorthogonal handles (azide/DBCO/TCO) with cleavable or non-cleavable linkers.

Typical inputs to start a project?

Target identity and matrix, desired application, known sequences (if any), affinity goals, required conjugations/labels, scale, purification, and QC expectations.

Speak to a Scientist

Tell us about your aptamer target and application. We’ll recommend selection strategy, stabilization, and conjugation to meet your performance goals.

Please avoid confidential details; we can arrange an NDA if needed.

Why Choose Bio-Synthesis

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