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Conjugation Chemistry

Lipid-Oligonucleotide Conjugates (LOCs)

Custom lipid-modified oligonucleotides — cholesterol, fatty acids, GalNAc, PEG-lipids, and phospholipids — engineered for enhanced delivery, stability, and tissue targeting.

Overview Lipid Conjugates Technology & Application Related Services FAQ Speak to Scientist

Overview

Bio-Synthesis provides comprehensive lipid oligo conjugation services (LOCs) for oligonucleotides, enabling improved pharmacokinetics, biodistribution, and cellular uptake of nucleic acid therapeutics. By attaching lipophilic moieties such as cholesterol, fatty acids, GalNAc-lipids, PEGylated lipids, phospholipids, and vitamins, we create custom conjugates optimized for siRNA, ASO, mRNA, aptamers, and DNA/RNA probes.

Sterol- and fatty acid-based conjugates increase membrane anchoring and serum stability; carbohydrate-targeted lipids like GalNAc ensure hepatocyte-specific delivery; PEG-lipid conjugates provide stealth and improve circulation half-life; phospholipids, dialkyl chains, and glycerides support liposomal or nanoparticle formulations; vitamin-lipids offer tissue-specific targeting and functional synergy.

We support research to regulated production, providing scalable synthesis, purification (HPLC/SEC), and QC (ESI-MS, MALDI, endotoxin, stability). Whether you need a cholesterol-conjugated siRNA, GalNAc-ASO for liver delivery, or a DSPE-PEG oligo for LNPs, our team delivers tailored solutions aligned with your therapeutic or diagnostic program.

Lipid Conjugates

Product Category Function Code
Cholesterol Sterol-Based Lipid Most common lipid used; enhances cellular uptake and stability [Chol]
Palmitic Acid (C16) Fatty Acid-Based Improves lipophilicity and membrane anchoring [C16]
Stearic Acid (C18) Fatty Acid-Based Saturated fatty acid; improves pharmacokinetics [C18]
Docosahexaenoic Acid (DHA) Fatty Acid-Based Enhances fusion, endosomal escape, brain/liver delivery; via LNPs, micelles, or direct conjugation [DHA]
Myristic Acid Fatty Acid-Based Enhances membrane interaction, uptake, and hydrophobicity [C14]
Oleic Acid (C18:1) Fatty Acid-Based Unsaturated fatty acid for increased membrane interaction [C18:1]
Linoleic Acid (C18:2) Fatty Acid-Based Polyunsaturated fatty acid for enhanced targeting [C18:2]
TriGalNAc-lipid Carbohydrate-Targeted High-affinity, multivalent hepatocyte uptake; siRNA, ASO, nucleic acid drugs [TriGalNAc]
GalNAc-lipid Carbohydrate-Targeted Dual functionality – liver targeting & membrane affinity [GalNAc]
DSPE-PEG2000 Lipid-PEG Conjugates Adds hydrophilicity & flexibility; common in LNPs [DSPE-PEG2000]
C16-PEG2000 Lipid-PEG Conjugates For micelle or nanoparticle delivery [C16-PEG2000]
Cholesterol-PEG2000 Lipid-PEG Conjugates Combines membrane targeting and stealth [Chol-PEG2000]
Steric Acid-PEG Lipid-PEG Conjugates Improves circulation half-life [C18-PEG]
1,2-Di-O-octadecyl-sn-glyceryl (DOG) Dialkyl Lipids Long-chain alkyl ether for strong hydrophobic interaction [DOG]
Diacylglycerol (DAG) analogs Phospholipid-Based Membrane anchoring; used in vaccine delivery [DAG]
Phospholipid (e.g., DSPE) Phospholipid-Based Common in liposome and LNP formulations [DSPE]
Triacylglycerol (TAG) analogs Glyceride-Based Enhance lipid bilayer integration [TAG]
Vitamin E (Tocopherol) Vitamin-Lipid Lipophilic antioxidant; liver targeting [VitE]
Vitamin D3 Vitamin-Lipid Enhances lipophilicity, membrane interaction, possible nuclear targeting [VitD3]

Need a lipid we didn’t list?

We routinely source or custom-synthesize lipid reagents and can align to your internal codes or vendor references.

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QC & Deliverables

QC & Deliverables

  • QC package: ESI-MS/MALDI identity, HPLC purity, SEC optional.
  • Release data: Yield (OD/µmol), purity %, lipid identity, spacer length, placement.
  • Supporting files: HPLC chromatograms, MS spectra, SEC traces (if ordered).
  • Optional: Endotoxin, moisture, stability, residual solvents.
  • Documentation: CoA with full details, storage & handling notes.
  • Formatting: Lyophilized tubes or plates; custom labels/barcodes.

Deliverables are provided digitally and archived for re-order traceability.

siRNA Lipid conjugate illustration

Lipid Conjugate Technology & Applications

Technology

  • Sterol and fatty acid conjugation: Cholesterol, C16, C18, DHA, and other fatty acids enhance membrane anchoring, uptake, and serum stability.
  • Carbohydrate-targeted lipids: GalNAc and TriGalNAc enable high-affinity hepatocyte uptake; widely used in siRNA/ASO therapeutics.
  • PEG-lipid conjugates: DSPE-PEG, C16-PEG, and Chol-PEG improve circulation half-life and support LNP/micelle formulation.
  • Phospholipids and glycerides: DSPE, DAG analogs, and TAG analogs enable liposome/LNP incorporation for vaccine and therapeutic delivery.
  • Vitamin-lipids: Tocopherol and Vitamin D3 add tissue-specific targeting and potential synergistic activity.

We integrate lipid moieties via NHS, maleimide, or click chemistry, or directly on solid support. PEG spacers are often added to reduce steric hindrance and preserve hybridization.

Applications

  • Therapeutics: Cholesterol- and GalNAc-modified siRNA and ASOs for systemic and liver-targeted delivery.
  • mRNA and LNPs: DSPE-PEG and phospholipid conjugates for nanoparticle and vaccine delivery platforms.
  • Diagnostics: Lipid-tagged probes for improved cell uptake in imaging and hybridization assays.
  • Surface immobilization: Lipid-anchored oligos for biosensors, micelles, or membrane-model systems.
  • Custom builds: Multi-functional conjugates combining lipids with dyes, peptides, or targeting ligands.

Our lipid conjugates are supplied with full QC (HPLC, MS, SEC optional) and scalable production, from nmol pilot lots to gram-scale cGMP supply.

FAQ

What scales and formats can you deliver?

From small research lots (nmol–mg) to large-scale and regulated production. Delivery as lyophilized oligos in tubes or plates, with optional buffer exchange and counter-ion adjustments.

Can you combine lipids with other conjugates (e.g., dyes, peptides, GalNAc)?

Absolutely. We routinely build multi-functional constructs (lipid + dye/peptide/GalNAc), using orthogonal chemistries and spacers to maintain performance.

Any guidance for in vivo use?

Choose lipids that match the target tissue and delivery route (e.g., GalNAc for liver). Validate PK/PD, assess immunogenicity, and consider LNP or micelle formulation for certain lipids (DSPE-PEG, DAG, phospholipids).

Which lipids do you recommend for siRNA vs. ASO?

siRNA: Cholesterol, GalNAc-lipids, DHA, and DSPE-PEG are common choices depending on delivery route (LNPs, micelles, or direct conjugation). ASO: Cholesterol, C16/C18 fatty acids, and GalNAc-lipids are frequently used for uptake and liver targeting.

5′/3′ vs. internal lipid placement — how do I choose?

Termini (5′/3′) minimize impact on hybridization and are easiest to QC. Internal placement is possible with appropriate spacers (e.g., PEG) but should be piloted to confirm Tm and activity.

Will lipid conjugation change duplex stability or activity?

Lipids can introduce steric effects. We typically add PEG spacers (PEG4–PEG12) to preserve hybridization and reduce self-association. A short pilot duplex is recommended for critical binding regions.

What conjugation chemistries do you support?

NHS–amine, maleimide–thiol, and click (azide/alkyne, SPAAC) are standard. We can integrate lipids on-solid support, or perform post-synthetic conjugation with orthogonal handle management.

Do you offer QC specific to lipid–oligo conjugates?

Yes. Identity by ESI-MS/MALDI, purity by HPLC, optional SEC for larger constructs, and documentation of lipid loading/substitution. Endotoxin and stability data are available on request.

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