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Targeted delivery chemistry • conjugation CDMO • U.S. manufacturing

Receptor-Targeted Oligonucleotide Conjugation

Custom ligand-conjugated siRNA, ASO, PNA, and PMO engineered for receptor-mediated uptake using small molecules, vitamins, carbohydrates, peptides, and custom targeting motifs — with site-specific 3′/5′/internal attachment and scalable Texas, USA manufacturing.

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siRNA • ASO • PNA • PMO 3′ / 5′ / internal attachment Small molecules • vitamins • carbohydrates • peptides Stable & cleavable linkers Texas, USA manufacturing
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Overview Ligand Classes Chemistry Modalities Manufacturing FAQs Recommended Reading Contact

Overview

Receptor-targeted oligonucleotide conjugates are constructs in which an oligonucleotide modality (siRNA, ASO, PNA, or PMO) is covalently linked to a receptor-binding ligand to support selective uptake and mechanistic studies. Ligand-directed conjugation can enable defined receptor engagement using small molecules, vitamins, carbohydrates, peptides, and custom targeting motifs.

Bio-Synthesis provides custom oligonucleotide–ligand conjugation with precise 3′, 5′, or internal attachment (design permitting). All synthesis, conjugation, purification, and analytical verification are performed in our Texas, USA facilities to support discovery through scalable program execution.

Site-specific attachment Custom ligand integration CMC-aware workflows
Conjugation portfolio

Related pages: GalNAc Conjugation • Lipid Conjugation • Peptide Conjugation

At a glance

Built for targeted delivery chemistry with manufacturing discipline.

Ligand Types

Small molecule • vitamin • carbohydrate • peptide

Modalities

siRNA • ASO • PNA • PMO

Placement
3′ / 5′ / internal
Linkers
Stable or cleavable
Analytics
LC‑MS + HPLC purity profiling
Location
Texas, USA manufacturing

Supported Targeting Ligand Classes

We support a broad range of receptor-targeting ligand classes and custom motifs. Ligand feasibility is evaluated based on functional handles, stability, and compatibility with the selected attachment site and purification strategy.

Small molecules: folate • integrin/PSMA ligands • GPCR motifs • client-supplied ligands • receptor uptake probes

Folate derivatives, integrin-binding ligands (RGD-like), PSMA ligands, GPCR-targeting motifs, hormone receptor ligands, kinase-binding motifs, and client-supplied small molecules.

Representative ligands Typical applications Manufacturing notes
Folate derivatives Receptor engagement & uptake screening Handle selection to preserve binding; linker/spacer tuning
Integrin ligands (RGD-like small molecules) Target validation; receptor bias studies Internal or terminal placement options; purification planning
PSMA ligands Receptor-mediated uptake models Site control important; stable vs cleavable linkers
Client-supplied small molecules Custom targeting programs Feasibility check: functional handle, stability, solubility

Vitamins & biotin: A · B-complex · C · D · E · K · biotin • vitamin conjugation • biotin conjugation • assay & capture

Representative payloads Drug type Typical function Conjugation notes
Vitamin E (α-, β-, γ-, δ-tocopherols; tocotrienols) Hydrophobic vitamins Membrane interaction, antioxidant biology, delivery studies Spacer-assisted conjugation (PEG/TEG or alkyl linkers) is commonly used to manage hydrophobicity and reduce aggregation during purification.
Vitamin A (retinoids), Vitamin D (calciferols), Vitamin K (phylloquinone/menaquinone) Fat-soluble vitamins Targeting, uptake, and mechanistic probes Typically conjugated via spacer/linker architectures to minimize steric interference and improve aqueous handling.
Vitamin B-complex: B1 (thiamine), B2 (riboflavin), B6 (pyridoxine), B12 (cobalamin) Water-soluble vitamins Receptor-mediated uptake, transport, and assay workflows Vitamin B12 conjugation uses defined peripheral handles to preserve intrinsic binding motifs; route selected to protect sensitive functional groups.
Vitamin C (ascorbic acid) Redox-active vitamin Stability and antioxidant mechanism studies Oxidation sensitivity is considered during route selection, purification, and storage; mild conditions preferred.
Biotin (vitamin B7), Folate (vitamin B9) Affinity / targeting handles Avidin/streptavidin capture, receptor targeting, immobilization Widely used for controlled stoichiometry conjugates; spacer length can be tuned for accessibility and assay performance.

Carbohydrates & multivalency: GalNAc • mannose • glucose • fucose • lactose • custom clusters • receptor/lectin engagement

Representative payloads Drug type Typical function Conjugation notes
GalNAc (mono- and triantennary) Carbohydrate targeting ligand Receptor-mediated uptake (ASGPR-focused programs) Supports 3′/5′/internal placement (design permitting). Multivalency and spacer engineering used to tune receptor engagement and handling.
Mannose / Mannosyl clusters Carbohydrate targeting ligand Lectin receptor engagement; uptake/probe studies Often benefits from PEG/TEG spacers to improve solubility and reduce nonspecific aggregation.
Glucose derivatives Carbohydrate motif Transport/uptake and mechanistic workflows Attachment chemistry selected to preserve key hydroxyl patterning; purification method chosen to maintain integrity.
Fucose / Lactose motifs Carbohydrate motif Receptor/lectin bias studies; assay tools Feasibility depends on functional handle availability; multivalent formats available where beneficial.
Custom multivalent carbohydrate constructs Multivalent targeting architecture Avidity-driven binding and uptake hypotheses Spacer and branching architectures can be optimized for manufacturability and batch consistency.

Peptides & receptor-binding motifs: RGD • TfR ligands • tumor-homing • CPP • custom peptides

Representative payloads Drug type Typical function Conjugation notes
RGD peptides and integrin-binding motifs Receptor-binding peptide Target validation and uptake studies Charge/hydrophobicity influences purification; spacer/linker chosen to balance receptor access and conjugate homogeneity.
Transferrin receptor (TfR) ligands / receptor-binding peptides Receptor-binding peptide Receptor-mediated uptake workflows Site selection minimizes steric clash with binding motif; linker design supports analytical confirmation and scale-up.
Tumor-homing peptides Targeting peptide Biodistribution and mechanistic probes Often paired with hydrophilic spacers to maintain solubility and reduce aggregation during purification.
CPP (cell-penetrating peptides) Uptake-enhancing peptide Cell entry and trafficking studies High cationic charge can shift chromatographic behavior; purification strategy is selected accordingly.
Client-designed peptides Custom peptide ligand Program-specific targeting hypotheses We accept client-supplied sequences or synthesize internally; feasibility review includes handle chemistry, stability, and purity targets.

Custom targeting motifs: client-supplied ligands • dual-ligand systems • multivalent architectures • proprietary motifs

Representative payloads Drug type Typical function Conjugation notes
Client-supplied small molecules / vitamins / ligands Custom targeting motif Program-specific receptor engagement Provide structure, handle chemistry (amine/thiol/click), purity and stability constraints; we design an attachment route compatible with your modality.
Dual-ligand constructs Multifunctional targeting architecture Co-targeting or avidity-driven uptake studies Spacer geometry and site placement are optimized to maintain binding and manage conjugate heterogeneity.
Multivalent formats (clusters / scaffolds) Multivalent targeting architecture Avidity-based receptor engagement Branching and spacer design selected for scalable synthesis and analytical resolution.
Proprietary targeting motifs Confidential ligand Custom workflows We support NDA-driven development; analytical confirmation and documentation tailored to stage (discovery → preclinical).

Attachment Chemistry & Site Control

Site control is a primary CQA for receptor-targeted conjugates. We engineer 3′, 5′, and internal attachment (design permitting), including strand-aware placement for siRNA duplexes, to preserve ligand binding, maintain modality performance, and support scalable purification.

3′ / 5′ Terminal
Terminal attachment

Fast lead iteration with clean analytical confirmation and robust purification routes.

Internal Site-defined
Internal attachment

Used when terminal placement conflicts with receptor binding or downstream design constraints.

Spacer PEG/TEG
Spacer engineering

Tune accessibility, solubility, and chromatographic behavior while preserving binding motifs.

Linker options (design dependent)

Stable linkers for handling and storage, or cleavable linkers for release hypotheses. We select routes compatible with ligand stability, oligo chemistry, and analytical confirmation.

CDMO deliverables

Designed for reproducible manufacturing, not just “one-off” conjugation.

  • Site definition (3′/5′/internal) documented per construct
  • Conjugation completeness strategy + analytical confirmation
  • Spacer/linker rationale aligned to binding + purification behavior
  • Batch homogeneity planning for scale-up workflows
Placement control

Strand-aware options (siRNA)

Scale-ready

Discovery → preclinical

Suggested inputs

Ligand structure/handle • preferred attachment site • spacer preference • stable vs cleavable • quantity & QC targets.

Modalities Supported

We manufacture ligand-conjugated constructs across multiple oligonucleotide modalities with CDMO discipline: controlled placement, batch consistency, and analytics suited for discovery through preclinical workflows. [2]

1
Design intake

Modality + ligand + attachment site + linker/spacer + QC targets.

2
Route selection

Chemistry chosen for ligand stability and purification behavior.

3
Build & purify

Conjugation + purification to resolve unconjugated/variants.

4
Verify

Identity/purity profiling + completeness confirmation.

CDMO program formats

  • Client-designed or client-supplied ligand integration
  • Single or multivalent ligand architectures (design dependent)
  • Attachment at 3′, 5′, or internal positions
  • Spacer tuning (PEG/TEG) to manage solubility and chromatography
Documentation

Route + placement + QC summary

Iteration speed

Lead screening support

Confidentiality

Client-supplied ligand support

QC bundle

Chromatograms + LC‑MS (as applicable)

Program add-ons
Spacer screen

PEG/TEG length comparison

Linker choice

Stable vs cleavable (design dependent)

Site screen

3′ vs 5′ vs internal (design permitting)

Batch summary

Route + placement + QC recap

Typical deliverables

COA (as applicable), chromatograms, LC‑MS confirmation, and batch summary aligned to project stage.

siRNADuplex
Ligand-conjugated siRNA

Strand-specific placement options with scalable duplex handling and analytics.

ASOSingle strand
Ligand-conjugated ASO

Gapmer or steric-block formats with controlled attachment and impurity planning.

PNA/PMOSpecialty
Ligand-conjugated PNA & PMO

Conjugation options tailored to backbone chemistry and downstream assay needs.

Manufacturing, Purification & Analytics

Conjugate manufacturing is managed around conjugate-specific CQAs: conjugation completeness, positional homogeneity, ligand integrity, and impurity profiles. Execution is performed in Texas, USA with scalable purification and analytics.

Purification Resolution
Conjugate purification

Separate unconjugated oligo, partially conjugated species, and positional variants when required.

Analytics Identity
Identity & purity confirmation

LC‑MS confirmation + chromatographic purity profiling selected per conjugate chemistry.

Controls Consistency
Batch reproducibility

Process controls selected to maintain conjugate homogeneity and predictable impurity behavior.

Scale-ready execution
  • Multi-scale capability: Seamless transition from exploratory milligram batches to multi‑gram manufacturing targets (program dependent).
  • Analytical gating strategy: Defined in‑process and post‑purification checkpoints to confirm conjugation completeness and positional integrity.
  • Scale-up engineering discipline: Purification and impurity management strategies selected with downstream reproducibility and batch homogeneity in mind.

Analytics & quality highlights

  • LC‑MS identity confirmation
  • HPLC/UPLC purity profiling
  • Conjugation completeness verification strategy
  • Impurity profile review (unconjugated/partial species)
  • Storage/handling guidance aligned to ligand sensitivity
Location

Texas, USA

Audience

Pharma & biotech

Related services

GalNAc • Lipid • Peptide

FAQ

Which oligonucleotide types can be conjugated to receptor-targeting ligands?

We support ligand conjugation for siRNA, ASO, PNA, and PMO modalities (design permitting).

What attachment positions are supported?

3′, 5′, and internal attachment are supported (design permitting). For siRNA duplexes, strand-specific placement can be aligned to design constraints.

Can you work with client-supplied ligands or proprietary targeting motifs?

Yes. Provide structure/sequence, functional handle (amine/thiol/click), purity, and stability constraints for feasibility evaluation.

Do you support stable and cleavable linkers?

Yes. Linker selection depends on mechanism goals, stability requirements, and analytical needs.

Where is manufacturing performed?

Oligonucleotide synthesis, conjugation, purification, and analytics are performed in our Texas, USA facilities.

Can you support spacer tuning for receptor accessibility and solubility?

Yes. PEG/TEG and custom spacer architectures can be used to tune sterics, solubility, receptor access, and chromatographic behavior.

More FAQ'sAll FAQ's

Talk to a Scientist

Share your modality (siRNA / ASO / PNA / PMO), receptor/targeting hypothesis, ligand class (small molecule / vitamin / carbohydrate / peptide), attachment site (3′/5′/internal), linker/spacer needs, purity/QC targets, and quantity. For client-supplied ligands, include handle chemistry, purity, stability constraints, and any solubility notes.

Custom ligand integration Site-specific placement Texas manufacturing Analytics-backed execution
What to include
  • Modality + sequence (and key modifications)
  • Ligand class + structure/sequence + handle chemistry
  • Attachment position (3′/5′/internal) + spacer preference
  • Stable vs cleavable linker preference
  • Quantity target + QC/purity expectations
Request a Quote Contact

Recommended Reading

Selected resources on oligonucleotide delivery and ligand-directed uptake concepts.

  1. Juliano R. The delivery of therapeutic oligonucleotides. Nucleic Acids Res. 2016;44:6518–6548.
  2. Dowdy SF. Overcoming cellular barriers for RNA therapeutics. Nat Biotechnol. 2017;35:222–229.
  3. Järver P, Langel Ü. Cell-penetrating peptides—A brief introduction. Biochim Biophys Acta. 2006;1758:260–263.
Want a tailored bibliography?

We can tailor recommended reading by receptor class and modality (siRNA/ASO/PNA/PMO) to support your internal review.

Why Choose Bio-Synthesis

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Greetings Researchers,

Please be advised that any information, guidelines, writeups, and oral/video/graphic content on our website are intended solely as general guidelines.
It is the researcher's sole responsibility to conduct thorough research on the designs of the products intended for their experiments before submitting
their designs to Biosynthesis for review of production feasibility.
Thank you for your understanding.

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