Custom conjugation of ssDNA/ssRNA, ASO, SSO, siRNA duplexes, PNA and PMO to antibodies, enzymes, carrier proteins and polymers—engineered for controlled loading (DAR‑like), site selectivity, linker behavior and analytical validation.
Oligonucleotide–macromolecule conjugates are covalent hybrids that pair the sequence specificity of DNA/RNA with the functional complexity of biologics or polymers. The macromolecule can provide targeting (e.g., antibody), pharmacokinetic extension (e.g., albumin/Fc), catalytic activity (enzyme), or physicochemical control (polymer scaffolds).1,2
A practical design mindset is to treat the conjugate as an architecture stack: (1) oligo modality and chemistry, (2) macromolecule selection, (3) conjugation site and ratio distribution, (4) linker behavior (stable vs cleavable), and (5) analytical confirmation of the critical quality attributes (CQA).3
Supported modalities include ssDNA, ssRNA, siRNA duplexes, ASO, SSO, PNA, and PMO formats with conjugation-ready handles (thiol/amine/azide/alkyne), site-selective protein modification workflows, purification, and analytics (SEC‑HPLC/LC‑MS/UV).
Define oligo‑to‑protein distribution and remove high‑load aggregates.
Reduce heterogeneity with cysteine, glycan, or enzymatic tagging routes.
Stable or cleavable (redox/pH) to match intracellular release needs.
Targeted RNA delivery (AOCs), PK extension (albumin/Fc), enzyme‑amplified detection, polymer-enabled multivalency/self‑assembly, and hybrid platforms for imaging and diagnostics.
We conjugate single‑ and double‑stranded oligonucleotide modalities to macromolecules. Handles can be installed on the oligo (thiol/amine/azide/alkyne) and/or on the macromolecule for orthogonal, modular assembly.
For duplex RNA, define which strand carries the conjugation handle and confirm duplex integrity post‑conjugation (gel/UV melting/LC‑MS strategy as feasible). For ss modalities, define whether 3′ or 5′ attachment is function‑tolerant.
Antibody–oligonucleotide conjugates (AOCs) adapt ADC-style architecture to nucleic acid payloads: defined loading distributions, site selectivity, and linker behavior to preserve binding while enabling intracellular exposure.1,2
Catalytically active hybrids for signal amplification, activation systems, and engineered detection or proximity platforms. Orientation, linker length, and activity retention are central CQA.
Use carrier proteins (e.g., albumin/Fc/transferrin) to tune half-life, biodistribution, and receptor engagement. Ratio and site selectivity are used to limit heterogeneity.3
Polymer scaffolds (PEG and beyond) can improve solubility, tune spacing/valency, enable self-assembly, and modulate biodistribution. Architecture choices include linear, branched, and multivalent formats.4
Smaller targeting proteins can improve tissue penetration and reduce Fc-driven effects while retaining specificity. Consider when IgG size or Fc biology is limiting.
Peptide–oligo conjugates (including CPP-like motifs) can be used as adjacent conjugation classes or self-assembling building blocks.5
Site-selective strategies reduce distribution breadth and improve batch reproducibility—critical when loading impacts binding, aggregation, or clearance.
Maintain intact conjugate structure for assay or surface applications.
Triggered in reducing intracellular environments (cytosol).
Cleavage in acidic endosomal/lysosomal compartments.
Program-specific protease recognition sequences for gated release.
Trigger-activated spacers that unmask payload after cleavage.
Define oligo modality, attachment site, desired loading range, and whether macromolecule release is required. Linker class and coupling route are selected accordingly.
Conjugate programs benefit from ADC‑style CQA discipline: define handle chemistry, linker class, loading distribution, free species limits, and aggregation thresholds. COA packages can be aligned to discovery vs preclinical needs with explicit lot traceability.
Our conjugation services are organized by macromolecule class and linker chemistry to streamline development workflows. Each platform is supported by defined coupling strategies, analytical validation, and scalable manufacturing options.
CPPs, endosome-active peptide domains, and peptide conjugation workflows with purification and LC‑MS confirmation.
ASGPR-targeted designs commonly paired with therapeutic oligo modalities.
Triggered release architectures (disulfide, acid‑labile) for intracellular de‑conjugation and payload release.
Pair macromolecule conjugation with modality manufacturing pages for chemistry/QC alignment: ASO manufacturing • siRNA manufacturing • splice‑switching oligos (SSO).
A covalent construct that links a synthetic DNA/RNA (ASO, siRNA, SSO, aptamer, probe) to a biologic or polymer (antibody, enzyme, carrier protein, PEG) to tune targeting, trafficking, PK, or assay performance.
We use site-selective handles (engineered cysteine, glycan remodeling, enzymatic tagging, orthogonal click reactions) plus purification and analytics (SEC-HPLC/LC-MS/UV) to quantify and tighten distributions.
Yes. Common classes include disulfide (redox‑sensitive), acid‑labile (pH‑triggered), protease‑cleavable linkers, and optional self‑immolative spacer modules. Linker selection is matched to stability requirements and the intended release compartment.
Common panels include SEC-HPLC (aggregation), IEX or RP-HPLC (purity), LC-MS (mass confirmation), UV/Vis ratioing, and gel-based methods (SDS-PAGE) where appropriate.
Yes. We support mixed backbone and 2′ chemistries, labels, and conjugation-ready handles (thiol, amine, azide, alkyne) on DNA/RNA and on the macromolecule.
Targeted delivery (e.g., antibody-directed uptake), PK extension (albumin/Fc), signal amplification and detection (enzyme/protein scaffolds), and polymer-enabled self-assembly or controlled release.
Share your macromolecule (antibody/enzyme/protein/polymer), intended loading range, and whether release is required. We’ll recommend site-selective chemistry, linker class, and an analytics plan.
For early feasibility, start with 2 builds: (1) a robust “baseline” coupling route, (2) a more site-selective route to tighten ratio distribution. Compare by aggregation + ratio + functional assay (binding/activity/knockdown as relevant).
Selected reviews and primary sources on antibody-, protein-, and polymer–oligonucleotide conjugation and site-selective bioconjugation.
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