Conjugation & Delivery

Oligonucleotide Delivery & Targeting Modifications

GalNAc for liver targeting, lipid & vitamin conjugates for CNS delivery, peptide & ligand strategies for oncology and immune cell targeting — plus linker chemistries and scalable manufacturing with ISO 9001/13485 quality systems.

Overview

Bio‑Synthesis designs and manufactures delivery‑enabled oligonucleotides with proven targeting strategies: GalNAc for hepatocytes, DHA/EPA & tocopherol for CNS‑leaning biodistribution, RGD/iRGD and folate for tumor homing, and mannose/lactose plus CPPs (TAT, Penetratin, R9) for immune and general uptake. We integrate conjugation, purification, full analytical QC, and documentation—scaled from discovery to bench‑to‑kilo supply under ISO 9001/13485 with RUO→GMP‑like workflows.

Typical placement uses the 3′ end via short PEG/TEG spacers to preserve hybridization and potency. We offer cleavable linkers (disulfide, Val‑Cit‑PAB, hydrazone, photocleavable PC) to tune release profiles and biodistribution for in vivo work. Manufacturing options include research grade through regulated documentation, with tubes, vials, or plate formatting.

45+ Years ISO 9001 / 13485 RUO → GMP‑like Bench → Kilo
Services at a glance
  • Design & conjugation: GalNAc, lipid/vitamin, peptide, ligand, CPP strategies
  • Linkers: PEG/TEG, disulfide, Val‑Cit‑PAB, hydrazone, photocleavable PC
  • Analytics: HPLC/UPLC, LC‑MS, OD260; optional endotoxin, residual solvents/moisture
  • Scale & packaging: research to kilo‑class; tubes, vials, plates

Liver Targeting — GalNAc

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Conjugate Description Typical Application Code
GalNAc (tri‑antennary) ASGPR ligand (3‑arm) Hepatocyte targeting; SC dosing [GalNAc3]
GalNAc (tetra‑antennary) ASGPR ligand (4‑arm) Enhanced avidity for liver delivery [GalNAc4]
Technical Notes
  • Prefer 3′‑end placement on the sense/passenger strand (siRNA) or 3′ of ASO with a short PEG/TEG spacer.
  • Evaluate partial PS, 2′‑OMe/2′‑F patterning, and seed‑region preservation in duplex formats.

CNS Delivery — Lipids & Peptides

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Conjugate Description Typical Application Code
DHA Omega‑3 fatty acid BBB‑leaning biodistribution; neuro delivery exploration [DHA]
EPA Omega‑3 fatty acid Anti‑inflammatory profile; tuning exposure [EPA]
Tocopherol Vitamin E derivative Stability; membrane interactions [Toco]
Angiopep‑2 LRP1‑binding peptide Receptor‑mediated BBB transport [Ang2]
RVG29 Rabies glycoprotein peptide Neuron targeting [RVG29]
Technical Notes
  • Keep antisense 5′ end clear (duplex formats) to preserve Ago2 loading; use PEG/TEG spacers for bulky conjugates.
  • Pilot formulation may improve biodistribution (e.g., pairing with 2′‑OMe/2′‑F patterning and terminal PS).

Oncology / Tumor Homing — Peptides & Ligands

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Conjugate Description Typical Application Code
RGD / iRGD peptides Integrin‑binding motifs Tumor homing; deep tissue penetration [RGD]/[iRGD]
Folate Vitamin B9 derivative Folate receptor‑positive tumors [FA]
Technical Notes
  • Pair with partial PS and 2′‑mods to balance affinity and safety; evaluate cleavable linkers for payload release.

Immune Cell Targeting — Glycans & CPPs

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Conjugate Description Typical Application Code
Mannose Mannose receptor ligand Macrophage/DC targeting [Man]
Lactose Lectin‑binding disaccharide Lectin‑mediated uptake [Lac]
CPPs (TAT, Penetratin, R9) Cell‑penetrating peptides General cellular delivery; extrahepatic tissues [CPP‑TAT]/[CPP‑PEN]/[CPP‑R9]
Technical Notes
  • Use short PEG/TEG spacers to reduce sterics; test conjugate orientation (5′ vs 3′) where biology allows.

Chemistry & Linkers

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Linker / Spacer Type Purpose Code
Short PEG / TEG Hydrophilic spacer Conjugate geometry; solubility; reduced sterics [TEG]
Cleavable Disulfide Redox‑sensitive Cytosolic release (reductive environment) [SS]
Val‑Cit‑PAB Enzyme‑cleavable Cathepsin‑triggered release [Val‑Cit‑PAB]
Hydrazone pH‑sensitive Endosomal release [Hydrazone]
Photocleavable PC Spacer Photo‑triggered Optically controlled release [PC‑Spacer]

Ask us about multivalency scaffolds (Trebler/Doubler, PAMAM) for avidity or multi‑payload designs.

FAQ

Where should I place conjugates like GalNAc, DHA, or RGD?

Commonly at the 3′ end via a short PEG/TEG spacer to preserve hybridization and reduce steric hindrance. Duplex formats keep the antisense 5′ end clear for Ago2 loading.

How do I choose between lipid/vitamin vs peptide vs glycan?

Start with tissue: liver→GalNAc; CNS→DHA/EPA/tocopherol/Angiopep‑2; tumor→RGD/iRGD or folate; immune→mannose/lactose/CPPs. Consider linkers and placement to balance exposure and potency.

Which QC and documentation can you provide?

HPLC/UPLC, LC‑MS, OD260 standard; optional endotoxin, residuals/moisture, and time‑scheduled stability. We support ISO 9001/13485 and RUO→GMP‑like documentation.

Can you format into plates or supply at kilogram scale?

Yes—tubes, vials, and plates with barcoding/labels are available. We scale from µmol screens to kilo‑class batches with consistent methods and release QC.

Need help selecting the best targeting strategy?

We’ll recommend conjugates, linkers, and placement—then align chemistries and QC for your route and scale.

Speak to a Scientist

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Why Choose Bio-Synthesis

Trusted by biotech leaders worldwide for over 40+ years of delivering high quality, fast and scalable synthetic biology solutions.