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Cell Delivery and Uptake
Lipophilic, vitamin, and GalNAc modifiers are often incorporated into oligos, such as siRNAs, ASOs, saRNAs, anti-microRNAs, to improve cell delivery and uptake.
We offer a wide range of hydrophobic modified phosphoramidites and CPGs for oligo incorporation at the 5’ and 3’ end, respectively.
Some of our 3’ lipophilic modifications are based on the natural sugar-phosphate backbone, which has the advantage to mitigate adverse structural effects on the oligo.
Many of our modifiers are available with all carbon-based or triethylene glycol (TEG) spacers and post-cell delivery cleavable linkers. A TEG spacer is often advantageous as it enhances solubility in acetonitrile.
We also offer oligonucleotide synthesis columns for incorporating our lipophilic modifiers at the 3’ end of your oligonucleotides.
Cholesteryl-conjugated oligonucleotides are attractive for use in antisense and other studies due to the lipophilicity and good availability of cholesterol. We have now developed products that use entirely plant-derived cholesterol, ensuring regulatory compliance with guidelines stating it is essential to use non-animal based products in pharmaceutical drug development for humans, making them even better choices for modification of oligos.
Vitamins (Vitamin E)
We offer a range of vitamin-based phosphoramidites. Vitamins that are not produced by the target cells can be internalised by cells after interacting with a specific binding protein, making them suitable for targeting specific cell types.Tocopherol has been utilised to target liver cells, improve the purification of ribozymes, as well as improve the purification of thiol-modified oligos.
Used similarly to cholesterol. Generating an oligonucleotide conjugate with a 5'-palmitoyl group attached through an amide bond has been shown to enhance the potency of telomerase inhibition.
An effective bioisostere of the natural 5′-monophosphate in small interfering RNAs (siRNAs). Metabolically stable 5’ vinyl phosphonate mimics 5’ phosphorylation, making them particularly useful when a sequence is incompatible with cellular kinases and cannot be 5’phosphorylated in-vitro.
GalNac conjugates improve hepatic drug delivery of liver-targeted nucleic acid therapeutics. Our GalNAc monomers can be used to build up flexible GalNAc clusters, varying in the number of GalNAc monomers and in their position within the oligo. Additionally, it is possible to add various spacers between each GalNAc monomer and to incorporate cleavable linkers between the oligo and the GalNAc cluster.