Payload-focused ODC support: cancer drug payloads, antibiotic payloads, delivery small molecules (PK/uptake modifiers), and endosomal escape agents for siRNA, ASO, DNA, PNA, and PMO constructs.
Oligonucleotide–drug conjugates (ODCs) are hybrid molecules in which a small-molecule payload is covalently linked to an oligonucleotide (e.g., siRNA, ASO, DNA, aptamer, PNA, or PMO) through a defined chemical linker.
In a typical ODC design, the oligonucleotide contributes sequence-specific recognition (gene silencing, splice modulation, or target binding), while the payload contributes a second pharmacologic function (e.g., cytotoxicity, antimicrobial activity) or a delivery function (e.g., uptake/PK modulation or endosomal escape enhancement). The linker model—stable vs cleavable—determines whether the payload must be released to function.
Route selection is driven by payload functional groups, stability, solubility, and the required release model.
Site selection (5′, 3′, or internal) reduces heterogeneity and preserves oligo function when properly planned.
Confirm identity/purity by HPLC/UPLC and LC-MS when feasible; report conversion/loading as appropriate.
Oligonucleotide–drug conjugates (ODCs) sit at the intersection of medicinal chemistry and oligonucleotide therapeutic design. Success depends on controlling three variables simultaneously: payload functional integrity, oligo biological compatibility (siRNA RISC loading / ASO RNase H or steric‑block behavior), and linker performance (stable vs trigger‑cleavable release).
We support defined, site‑specific conjugation on siRNA, ASO, DNA, aptamers, PNA, and PMO with controlled loading targets, purification, and QC aligned to your application. Typical projects include oncology payload conjugates, antibiotic payload conjugates, and delivery‑active small molecules used to tune biodistribution or improve endosomal escape.
If you share the payload structure and your intended release model, we’ll recommend a practical attachment site, spacer length, and coupling route.
Bio-Synthesis provides oligonucleotide–drug conjugation services (ODCs) for discovery and preclinical programs. We support siRNA and ASO drug conjugates[1,3] with site-defined attachment, stable or cleavable linker strategies (structure-dependent), purification, and fit-for-purpose analytical characterization.
Build ODCs around your oligo modality, payload structure, attachment constraints, and intended biology.
Choose stable vs cleavable chemistry depending on whether intracellular payload release is required.
HPLC/UPLC profiles; LC-MS when feasible; optional stability or conversion reporting (structure-dependent).
Expand each category for representative payloads and practical notes. Payload feasibility is chemistry-dependent and driven by functional groups, stability, solubility, and the desired linker/release model.
Tip: For duplex siRNA, specify whether the payload is intended on the sense strand, antisense strand, or a terminus-specific position.
Note: Uptake into bacteria is often the limiting factor. Share your intended delivery strategy (CPP, nanoparticle, etc.) so the construct is designed accordingly.
Tip: If you need “delivery without drug activity,” classify the payload as a delivery modifier rather than a therapeutic drug payload.
Endosomal escape is often the dominant barrier for functional delivery. If you share your cell model and target tissue, we can recommend a practical design direction.
ODC feasibility depends on payload functional groups, oligo modification site, stability, and solubility.[1,2,3] We plan the conjugation route to minimize heterogeneity and align purification/QC to your intended use.
Efficient coupling using 5′/3′ thiol or a thiolated internal position.
Bioorthogonal coupling using azide/alkyne or DBCO handles; SPAAC avoids copper exposure.
Direct carboxyl–amine coupling using a unique 5′/3′ amine (or payload amine).
Used when payload release is required for activity or to reduce on-target steric burden.
Preferred when stable permanent linkage is desired (e.g., uptake/PK modifiers or mechanistic studies).
Common for siRNA sense-strand designs or ASO termini; minimizes interference with base pairing when planned.
Often used to preserve 5′ requirements (e.g., siRNA antisense loading considerations).
Used when terminal attachment is constrained; requires careful placement to preserve function.
For duplex siRNA, specify strand (sense vs antisense), terminus (5′ vs 3′), and whether the payload should be compatible with RISC loading. We can also support asymmetric designs and spacer variants for screening.
Oligo sequence/modality • payload structure/handle • linker/release goal • loading target.
Site-defined coupling • stable vs cleavable selection • route chosen for payload integrity.
HPLC/UPLC • LC-MS when feasible • conversion/loading report • documentation.
If your decision depends on stability or release, share that goal so methods can align to it.
Duplex siRNA builds, end modifications, and screening formats.
Phosphorothioate patterns, 2′ sugar variants, and steric‑block formats.
Disulfide, pH‑labile, enzyme‑cleavable, and self‑immolative designs.
Defined ligand attachment for targeted delivery programs.
Cell‑penetrating peptides, targeting peptides, and spacer designs.
HPLC/UPLC, LC‑MS when feasible, and orthogonal confirmation options.
Send the oligo sequence/modality (siRNA/ASO/etc.), desired attachment site (5′/3′/internal and strand for siRNA), payload name/structure (or catalog number), stable vs cleavable preference (if any), quantity/purity targets, and intended use.
Yes. Cleavable linkers (e.g., disulfide, pH-labile, enzyme-cleavable) are supported when payload release is required (feasibility-driven).
This is goal-dependent. Many designs place delivery-active payloads on the sense strand (often 3′), while preserving antisense features needed for RISC loading.[1,2,3] We can provide spacer/position variants for screening.
Yes (feasibility-driven). Hydrophobic payloads often require spacer/linker planning and solvent-aware purification/QC methods.
For the fastest quote, share your oligo sequence/modality, payload name/structure (or catalog number), desired attachment site (and strand/terminus for siRNA), stable vs cleavable preference, quantity/purity targets, and intended use. We’ll recommend a practical route plus purification/QC aligned to your application.
If you’re unsure which coupling is best, send the payload structure—route selection is driven by functional groups and stability constraints.
What happens next: We review feasibility, recommend handle/linker options, confirm QC deliverables, and provide pricing.
Citations are provided as entry points for background and design rationale (payload release, biodistribution, uptake, trafficking, and endosomal escape). For payload-specific chemistry precedent, we can provide a targeted bibliography aligned to your exact drug/linker.
Clients typically engage us for dual-mechanism oncology conjugates, antibiotic–antisense platforms, delivery-modulating small-molecule attachment, and linker optimization strategies designed to balance stability and intracellular release.
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