Site-specific lipid conjugation to tune biodistribution, uptake, and pharmacokinetics—supporting siRNA duplexes and ASO single-strands. Supported from early discovery through gram- to multi‑kilogram scale manufacturing with CMC-aligned workflows.
Lipid conjugation is a practical lever to tune hydrophobicity, plasma protein binding, tissue distribution, and cellular uptake for oligonucleotide therapeutics. We support lipid conjugation for siRNA duplexes and ASO single-strands, with site-specific attachment strategies selected to preserve functional regions and align with analytical verification.
Common designs include cholesterol/sterol conjugates, saturated and polyunsaturated fatty acids (e.g., DHA/EPA), tocopherol, PEG-lipid hybrids, and custom client-supplied lipids. Attachment can be engineered at the 3′ terminus, 5′ terminus, or internally (where design permits) for both siRNA and ASO programs.
Quick facts
Lipid choice and linker strategy should be matched to modality, target tissue, dosing route, and stage (discovery vs preclinical).
Cholesterol & analogs
C12–C24; saturated/PUFA
How we align lipid-conjugate design with manufacturing and analytics.
Define position (3′/5′) and linker/spacer to preserve activity and enable clean analytical confirmation.
Compare sterols, fatty acids, and PEG-lipid hybrids across uptake and exposure readouts.
Track conjugation completeness, positional species, and impurity profiles to reduce rework during scale-up.
Representative lipid classes and examples used for conjugation to oligonucleotides (siRNA & ASO). Client-supplied lipids can be evaluated based on functional handle, purity, and compatibility.
Attachment strategy is selected to preserve function and maintain manufacturability. For siRNA duplexes, specify strand and position requirements; for ASOs, confirm terminus selection and compatibility with the intended mechanism.
A common, robust format for both siRNA and ASO designs; supports linker/spacer tuning.
Useful when compatible with functional requirements; confirm activity impacts for modality.
Evaluated where design permits and analytical confirmation remains unambiguous.
Lipid conjugates add critical quality attributes: conjugation completeness, linker integrity, positional homogeneity, and conjugate-specific impurities. We align purification and analytics to program stage to support scale-up without redesign.
Resolve unconjugated oligo, partially conjugated species, and positional variants when relevant.
Orthogonal confirmation of conjugation and purity (e.g., LC‑MS and chromatography profiles).
Assess storage and handling stability for linker and conjugate integrity to support shipping and use.
Tell us your modality (siRNA or ASO), target tissue/route, lipid(s) of interest (or ask us to propose options), attachment position, and linker/spacer preferences. If using a client-supplied lipid, include structure/handle and purity.
Yes. We support lipid conjugation for siRNA duplexes and ASO single-stranded oligonucleotides with program-appropriate attachment strategies.
Yes. Cholesterol is a sterol, which is a major class of lipids commonly used as a hydrophobic conjugation motif.
Often yes. Provide the lipid structure or catalog number, functional handle, purity, and any constraints; we will assess compatibility and propose an attachment method.
Most programs use 3′ or 5′ terminal attachment. Internal placement can be evaluated when compatible with the modality and analytical strategy.
Suggested starting points on oligonucleotide delivery and conjugate strategies (siRNA and ASO).
Citations can be added inline depending on how you want to attribute claims.
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