CDMO-ready folate conjugation for folate receptor-mediated targeting. Manufacturing support for folate‑conjugated siRNA and ASO, plus PNA and PMO—with defined 3′/5′/internal placement, custom linkers, and analytics designed for scale.
Folate (vitamin B9) is a small-molecule ligand recognized by folate receptors (FRα/FRβ) that are enriched on selected cell types and many tumor models. By attaching folate to an oligonucleotide, developers can explore receptor-mediated uptake and targeted exposure in discovery and preclinical studies. 1
Folate conjugation is commonly used as a screenable targeting motif to compare ligand density, attachment site, and linker stability across in vitro uptake assays and in vivo biodistribution studies. We support stable or cleavable linkers and defined 3′/5′/internal placement for multiple oligo modalities.
Bio-Synthesis supports folate conjugation for siRNA duplexes and single-stranded modalities (ASO, PNA, PMO) with position-specific attachment and purification/analytics designed to verify conjugation completeness and product identity.
Quick facts
Folate receptor binding can enable receptor-mediated uptake; linker and placement choices influence stability, handling, and bioactivity.
Receptor targets
High density ligand
Core considerations for discovery-to-preclinical folate conjugate development.
A practical targeting handle to evaluate uptake and exposure patterns in FR-expressing systems.
Defined placement (3′/5′/internal) with stable or cleavable linkers aligned to modality and mechanism.
Purification and analytics designed to resolve unconjugated/partial conjugates and support scale-up.
Folate receptor alpha (FRα) is overexpressed in multiple solid tumor models including ovarian, lung, breast, and certain colorectal cancers, while limited expression is observed in most normal tissues. FRβ is reported in activated macrophages and selected hematologic contexts. This differential expression pattern makes folate a practical small‑molecule ligand for receptor‑mediated targeting studies in oncology and inflammation models.
Folate receptors bind folate and can mediate endocytosis. In receptor-targeting studies, folate conjugation is used to bias uptake toward FR-expressing cells and compare design variables such as linker stability, attachment site, and ligand presentation. 2
Folate binds folate receptors (FRα/FRβ) to initiate uptake in receptor-positive systems.
Receptor binding can trigger internalization; linker/chemistry can influence trafficking and stability.
Oligo modality and chemistry govern where activity occurs (cytosol/nucleus) after uptake.
Schematic representation of folate receptor binding, endocytosis, and intracellular delivery of folate-conjugated oligonucleotides.
Compare uptake in FR‑positive vs FR‑negative models and optimize ligand density and placement.
Profile exposure patterns and tissue distribution across linker types and conjugate architectures.
Assess receptor-targeted delivery hypotheses in tumor-relevant systems with defined QC attributes.
Study internalization/trafficking behavior and stability windows using stable vs cleavable linkers.
Folate conjugates can be configured as terminal or internal attachments and paired with modality-appropriate chemistry. Programs may evaluate single folate ligands, spacer-assisted constructs (e.g., PEG/TEG), or client-supplied folate variants when required. 2
Common format for receptor-targeting evaluation and uptake studies.
Best for: screening
Spacer architectures can tune presentation, hydrophilicity, and handling.
Best for: developability tuning
Folate‑conjugated siRNA with defined strand/terminal placement options, scalable duplex handling, and analytics.
Best for: gene silencing
Folate‑conjugated ASO (gapmer or steric‑block) with controlled attachment, impurity planning, and QC support.
Best for: antisense programs
Conjugation tailored to backbone chemistry and downstream assay needs.
Best for: specialty modalities
We can incorporate client-provided ligands or custom targeting motifs per program design.
Best for: differentiated IP
Linker choice and attachment site influence conjugation stability, purification behavior, and biological performance. Programs often compare stable linkers versus cleavable designs depending on desired release and assay interpretation. 3
Designed to maintain conjugate integrity during handling and circulation; supports clear interpretation of distribution.
Consider: sterics & purification
Designed to release the active oligo under defined triggers; route selection considers stability windows.
Consider: stability window
Position-specific attachment can be selected to preserve functional regions, manage duplex loading (siRNA), and align with nuclease protection and analytical strategy. We support 3′, 5′, and internal placement depending on modality and design intent.
Common folate activation strategies include EDC/NHS-mediated coupling of carboxyl groups, spacer-enabled PEG or TEG linkers to improve solubility, and alternative chemistries such as click-based conjugation for defined attachment control. Chemistry selection is guided by solubility, stability, and downstream analytical resolution requirements.
Spacer architectures (PEG/TEG, tuned alkyl spacing) are selected to manage aggregation and preserve handling.
Purification strategies are designed to resolve unconjugated oligo, partial conjugates, and positional variants where relevant.
Stable vs cleavable linkers are selected against assay intent; stability profiling supports storage and study conditions.
Defined CQAs and analytics are carried from early batches through scale-up to reduce surprises later.
Define modality, attachment site (3′/5′/internal), linker type, and analytical strategy.
Solid-phase synthesis with modification control and in-process verification.
Activation and covalent attachment using selected chemistry platform.
Resolve conjugated vs unconjugated species; confirm identity via LC‑MS and chromatographic methods.
Batch documentation and scalable execution aligned to preclinical development needs.
Folate conjugates introduce additional CQAs: conjugation completeness, linker integrity, ligand stoichiometry, and conjugate-specific impurities. A development-aligned workflow defines these attributes early and carries them across scale. 3
Resolve unconjugated oligo, partially conjugated species, and positional variants where relevant.
Confirm conjugation and composition via orthogonal assays (e.g., LC‑MS and chromatography profiles).
Evaluate linker/conjugate stability under storage and handling conditions to support shelf-life and shipping.
Small molecules, vitamins, carbohydrates, and custom motifs for receptor-mediated targeting programs.
Cholesterol and advanced lipid conjugates for delivery studies with 3′/5′/internal placement options.
Client-designed peptides or CPPs conjugated to siRNA, ASO, PNA, or PMO with full site control.
Hepatocyte targeting conjugation including single and tri-GalNAc formats with scalable synthesis.
Site-specific oligonucleotide conjugation to monoclonal antibodies and fragments for targeted delivery and ADC-style architectures.
Covalent attachment of cytotoxic drugs, payloads, or functional small molecules to siRNA, ASO, PNA, or PMO with defined linker control.
Tell us your modality (siRNA, ASO, PNA, PMO), target biology and model system, and preferred folate architecture (attachment site, linker type, and any client-supplied ligand requirements). We’ll help translate design intent into a manufacturing-ready conjugate plan.
Yes. Folate (vitamin B9) is a small-molecule ligand used to engage folate receptors and explore receptor-mediated uptake in receptor-positive systems.
We support folate conjugation for siRNA, ASO, PNA, and PMO programs with defined placement and modality-appropriate chemistry.
Commonly at 3′ or 5′ termini; internal placement can also be supported depending on modality, functional regions, and analytical strategy.
Conjugation completeness, linker integrity, and resolution of unconjugated or partially conjugated impurities; identity confirmation via orthogonal analytics (e.g., LC‑MS and chromatography).
Selected publications relevant to folate receptor targeting, ligand conjugation, and oligonucleotide delivery chemistry.
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