Cholesteryl TEG Modified Oligonculeotide
Bio-Synthesis offers cholesteryl TEG (15 atom triethylene glycol spacer) modified oligonucleotide synthesis services. Contact us for Cholesteryl TEG modified oligonucleotide synthesis.
Since oligonucleotides are predominantly hydrophilic, they tend to have difficulty permeating cell membranes. In order to improve cellular uptake, one strategy is to conjugate to oligonucleotides molecules that are non-toxic and hydrophobic. Cholesteryl conjugated oligonucleotides have been the subject of great interest in antisense and other studies. The addition of cholesterol has been shown to enhance the penetration of oligonucleotides into the cells1, probably due to lipophilic nature of the cholesterol molecule. It has been used as a transfection aid for antisense oligos and siRNAs, both in vitro and in vivo. 3’-Cholesterol containing oligonucleotides exhibited significant 3’-endonuclease resistance.2-4 Cholesterol is a very hydrophobic modification that is best purified using RP-HPLC.
Cholesterol TEG (Triethylene Glycol) modifications are widely used in oligonucleotide design. Adding cholesterol to oligonucleotides enhances delivery into cells and increases their lipophilicity. Cholesterol TEG-modified oligonucleotides serve several vital functions, particularly in enhancing the performance and efficiency of oligonucleotide-based therapies and research applications.
Cholesterol TEG oligonucleotide modifications effects:
Improved Cellular Uptake
Cholesterol is a lipophilic molecule that interacts with lipid bilayers of cell membranes. Cholesterol modifications facilitate better cellular uptake of antisense or siRNA oligonucleotides. Cholesterol modifications are especially useful in therapeutic applications where efficient delivery to target cells is critical.
Enhanced Stability
The cholesterol moiety increases the stability of the oligonucleotide in biological systems, reducing degradation by nucleases and leading to a prolonged circulation time and sustained activity.
Improved Membrane Permeability
Cholesterol facilitates the interaction of oligonucleotides with lipid-rich cell membranes, improving their uptake into cells to enable efficient delivery to intracellular targets. Cholesterol modifications are especially useful in delivering therapeutic oligonucleotides such as siRNAs, antisense oligonucleotides, or aptamers into cells.
Targeting Specific Tissues
Tissues rich in lipoproteins preferentially take up Cholesterol-conjugated oligonucleotides, such as the liver, allowing targeted delivery of the oligonucleotide therapeutic to specific tissues.
Conjugation for Drug Delivery
Cholesterol TEG-modified oligonucleotides can be conjugated to liposomes or other lipid-based delivery vehicles to improve their delivery efficiency in drug formulations.
Enhancing Lipophilicity
The addition of a cholesterol modification increases the overall lipophilicity of the oligonucleotides. The cholesterol modification is compatible with lipid-based delivery systems or aiding in crossing biological barriers like cell membranes or the blood-brain barrier.
Applications in Antisense and siRNA Therapies
Therapeutic antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) often utilize cholesterol modifications for gene silencing therapies. Cholesterol modification improves the therapeutic potential by enhancing bioavailability and reducing off-target effects. Incorporating a Cholesterol TEG modification into your oligonucleotide design will help improve its delivery and stability.
Product Information
Cholesteryl TEG Modified Oligonculeotide
End Modifier, Antisense, siRNA, Cell Penetration
-20°C To -70°C
Oligonucleotides are stable in solution at 4°C for up to 2 weeks. Properly reconstituted material stored at -20°C should be stable for at least 6 months. Dried DNA (when kept at -20°C) in a nuclease-free environment should be stable for years.
References/Citations:
- M.K. Bijsterbosch, et al., Nucleic Acids Res., 2000, 28, 2717-2725.
- M.K. Bijsterbosch, et al., J. Pharmacol. Exp. Ther., 2002, 302, 619-626.
- M. Manoharan, Antisense Nucleic Acid Drug Dev, 2002, 12, 103-28.
- M. Manoharan, Curr Opin Chem Biol, 2004, 8, 570-9.
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