When conjugated to oligonucleotide drugs, Triantennary N-Acetylgalactosamine (GalNAc) enhances their specific delivery to targets in liver cells. Already, the FDA has approved several GalNAc-conjugated oligonucleotides for clinical use.
The ligand of the asialoglycoprotein receptor (ASGPR), triantennary N-acetylgalactosamine (tri-GalNAc), when conjugated to oligonucleotides, improves their cellular uptake and tissue-specific delivery. ASGPR binds glycoproteins with terminal galactose residues in liver cells and removes targeted glycoproteins from circulation. The half-life of therapeutic GalNAc-RNAi drugs is relatively long, allowing monthly to half-yearly dosing regiments.
The conjugation of siRNAs to multivalent GalNAc linkers enhances their delivery and gene silencing in liver cells. GalNAc linkers attached to the 3'-end of siRNA sense strands allow delivery into cells without additional delivery reagents. GalNac-conjugates oligonucleotides exhibit improved tissue-specific delivery for antisense oligonucleotides (ASOs) and siRNAs.
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" Bio-Synthesis provides custom synthesized GalNAc-conjugated oligonucleotides including GalNAc-siRNAs.
Bio-Synthesis also provides a full spectrum of high quality custom oligonucleotide modification services including back-bone modifications, conjugation to fatty acids, biotinylation by direct solid-phase chemical synthesis or enzyme-assisted approaches to obtain artificially modified oligonucleotides, such as BNA antisense oligonucleotides, mRNAs or siRNAs, containing a natural or modified backbone, as well as base, sugar and internucleotide linkages.
Bio-Synthesis also provides biotinylated and capped mRNA as well as long circular oligonucleotides".
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