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Oligo Modifications for Cell Delivery & Uptake

Boost cellular internalization with peptide, lipid, glycan, and ligand strategies—plus nucleoside lipidations, endosomal‑escape peptides, PEG/TEG spacers, and cleavable linkers Delivered under ISO 9001/13485 quality with RUO→GMP‑like workflows.

45+ Years ISO 9001 / 13485 RUO → GMP‑like Bench → Kilo
Overview Strategies & Codes FAQ Speak Services

Overview

Bio‑Synthesis engineers delivery‑enabled oligonucleotides that reach cells efficiently and preserve activity. We combine peptides (CPPs, NLS), lipids/vitamins (cholesterol, 2′‑O‑C16, tocopherol), glycans/ligands (mannose, lactose, RGD/iRGD, folate, B12), and spacers/linkers (PEG/TEG, cleavable SS / Val‑Cit‑PAB / hydrazone / PC) to tune uptake, trafficking, and payload release.

With 45+ years of experience, ISO 9001/13485 quality, and RUO→GMP‑like workflows, we support ssDNA/dsDNA, ssRNA, and siRNA formats—from feasibility to bench‑to‑kilo supply—pairing design help, conjugation chemistry, purification, and full analytical QC (HPLC/UPLC, LC‑MS, OD260; optional endotoxin/residuals/stability).

CPPs Cholesterol / 2′‑O‑C16 Mannose / Lactose RGD / Folate / B12 PEG/TEG Spacers Cleavable Linkers ISO 9001/13485 Bench → Kilo
Services at a glance
  • Design & Conjugation: handle selection, CPP/lipid/glycan choice, placement & density optimization.
  • Spacers & Release: PEG/TEG geometry; cleavables (SS, Val‑Cit‑PAB, hydrazone, PC) for intracellular release.
  • Formats: ssDNA/dsDNA, ssRNA, siRNA; tubes, vials, plate formatting with barcodes/labels.
  • Analytics & QC: HPLC/UPLC, LC‑MS, OD260; optional endotoxin, residuals, stability studies.
  • Scale & Documentation: µmol screens → kilo‑class; ISO 9001/13485; RUO→GMP‑like files.

Strategies & Codes

Cell‑Penetrating Peptides Lipids & Vitamins Nucleoside Lipidations Glycans & Ligands Endosomal Escape Spacers & Linkers Multivalency & Scaffolds
Product / Conjugate Description Application Code
Cell-Penetrating Peptides (CPPs)
TAT Arginine-rich peptide General cellular uptake [CPP-TAT]
Penetratin Homeodomain-derived peptide Endocytic/translocation pathways [CPP-PEN]
Poly-Arg (R9) Poly-arginine peptide High uptake CPP [CPP-R9]
Transportan / Pep-1 Amphipathic CPPs Delivery of diverse cargos [CPP-TP]/[CPP-P1]
NLS Peptides Nuclear localization signal Nuclear uptake for AON/SSO [NLS]
Lipids & Vitamins
Cholesterol Hydrophobic sterol Uptake enhancement [Chol]
Tocopherol Vitamin E derivative Antioxidant stability; robustness [Toco]
Stearic / Palmitic / Oleic C18:0 / C16:0 / C18:1 fatty acids Hydrophobic anchoring [SA]/[PA]/[OA]
Diacylglycerol (DAG) Lipid anchor Membrane association [DAG]
Squalene Highly hydrophobic terpenoid Self-assembly into particles [SQL]
Phosphatidylethanolamine Lipid headgroup Anchoring; endosomal release [PE]
Ceramide Sphingolipid Endolysosomal trafficking [Cer]
Nucleoside Lipidations
2′-O-C16 (A/C/G/U) Hexadecyl lipidated nucleosides Membrane interaction; extrahepatic delivery [C16-2-O-A/C/G/U]
2′-O-Stearyl (C18) Stearyl-modified nucleosides Hydrophobic anchoring [C18-2-O-A/C/G/U]
2′-O-Oleyl (C18:1) Oleyl-modified nucleosides Delivery efficiency; flexibility [C18:1-2-O-A/C/G/U]
Glycans & Ligands
Mannose Mannose receptor ligand Macrophage/DC targeting [Man]
Lactose Lectin-binding disaccharide Lectin-mediated uptake [Lac]
RGD / iRGD Integrin-binding peptides Tumor homing & penetration [RGD]/[iRGD]
Folate Folate receptor ligand Receptor-positive cells [FA]
Vitamin B12 (Cobalamin) Receptor ligand Receptor-mediated uptake [B12]
Albumin-binding tag Serum albumin interaction PK extension; passive targeting [ABP]
Endosomal-Escape Peptides
INF7 HA2-derived fusogenic peptide Endosomal disruption [INF7]
GALA pH-responsive amphipathic peptide Endosomal release [GALA]
KALA / Hn Lysine/histidine-rich peptides pH-buffering, membrane interaction [KALA]/[Hn]
Spacers & Cleavable Linkers
Short PEG / TEG Hydrophilic spacer Conjugate geometry; solubility [TEG]/[PEG]
Cleavable Disulfide Redox-sensitive linkage Release in cytosol [SS]
Val-Cit-PAB Cathepsin-cleavable linker Enzyme-triggered release [Val-Cit-PAB]
Hydrazone pH-sensitive linkage Endosomal release [Hydrazone]
Photocleavable (PC) Spacer Light-triggered On-demand release [PC-Spacer]
Multivalency & Scaffolds
Multivalent Trebler / Doubler 3- or 2-arm branchers Valency increase; avidity [Trebler]/[Doubler]
PAMAM Dendrimer Branched polymer scaffold High payload density [PAMAM]
  • Placement: Prefer 3′ conjugation via short PEG/TEG spacers; keep antisense 5′ end clear in duplex designs.
  • Balance: Avoid over‑lipidation or excessive CPP density that can reduce potency or increase toxicity.
  • Release: Pair with cleavable linkers (SS/Val‑Cit‑PAB/hydrazone) to improve intracellular availability.

Services & Capabilities

Services at a Glance

  • Design & conjugation: CPPs, lipids/vitamins, glycans/ligands, nucleoside lipidations; 3′‑end placement with PEG/TEG spacers.
  • Linkers & release: Disulfide (redox), Val‑Cit‑PAB (enzyme), hydrazone (pH), photocleavable PC; multivalency (Trebler/Doubler, PAMAM).
  • Analytics & QC: HPLC/UPLC, LC‑MS, OD260; optional endotoxin, residuals, time‑scheduled stability.
  • Scale & packaging: Discovery µmol → bench‑to‑kilo; tubes, vials, plates with labels/barcodes.
  • Documentation: ISO 9001/13485 quality; RUO→GMP‑like workflows & CoAs for tech transfer.
Design & Conjugation

Sequence review, handle selection, conjugation density/placement, and spacer length optimization.

Delivery Chemistries

CPPs (TAT/R9/Penetratin), cholesterol/tocopherol, 2′‑O‑C16/C18, mannose/lactose, RGD/iRGD, folate, B12.

Linkers & Release

SS, Val‑Cit‑PAB, hydrazone, photocleavable PC; Trebler/Doubler and PAMAM for avidity or payload density.

Analytics & QC

Method‑matched HPLC/UPLC and LC‑MS; OD260; optional endotoxin/residuals; stability timepoints.

Scale & Packaging

µmol screens → kilo‑class; tubes, vials, plates with barcodes/labels; concentration normalization.

Documentation & Support

ISO 9001/13485; RUO→GMP‑like documentation; scientist‑to‑scientist support and quoting.

Need help choosing a delivery strategy?

We’ll recommend conjugates, spacers, and linkers—and tune placement and density for your target and route.

Speak to a Scientist Browse All Modifications

FAQ

Which approach should I try first—CPPs or lipids?

Start with cholesterol or a short CPP (TAT/R9/Penetratin) plus a PEG/TEG spacer. Test 3′ placement; for duplexes keep the antisense 5′ end free for RISC/Ago2.

Where do I place the conjugate on siRNA/ASO?

Commonly the 3′ end (sense for siRNA, 3′ of ASO) via short PEG/TEG to reduce steric hindrance; validate activity with and without linkers.

How do I improve endosomal release?

Add fusogenic or pH‑responsive peptides (INF7, GALA, KALA/Hn) and/or use cleavable linkers (SS, Val‑Cit‑PAB, hydrazone) to promote cytosolic availability.

Can you supply plates and barcoded panels?

Yes—tubes, vials, and plates with barcodes/labels, normalized concentrations, and full CoAs are available for screening workflows.

Speak to a Scientist

Please avoid confidential details; we can arrange an NDA if needed.

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