GalNAc, or N-acetylgalactosamine, is an amino sugar derivative of galactose that can recognize and bind to a cell surface protein, the asialoglycoprotein receptor (ASGPR), which is abundantly expressed on liver cells (hepatocytes). The binding affinity to the receptor increases exponentially if several GalNAc units are combined into a multivalent ligand. The affinity of the ASGPR for a trimer of GalNAc is 1,000-fold higher than a dimer or monomer. GalNAc technology has largely as an alternative of LNP delivery for liver disease targets. The GalNAc-conjugated siRNAs are used to treat a variety of diseases, including cancer, viral outbreaks, and Parkinson's Disease. Three GalNA-siRNA conjugates, namely, Lumasiran (2020), Inclisiran (2021), and Vutrisiran (2022), have been approved by FDA and introduced to the market.
In BroadPharm, we provide different active groups (Maleimide, Thiol, NHS, Amine, Azido, DBCO, Alkyl, TCO, Tetrazine, etc.) functionalized trivalent GalNac for versatile bioconjugations. We also offer GalNac-Lipid as upgraded LNP composites for hepatic specific LNP delivery systems. Our trivalent GalNAc, meaning that three GalNAc molecules are clustered and conjugated to one cargo molecule. This setup guarantees high affinity of the interaction between ASGPR and the GalNAc ligand, thus promoting optimal efficiency of cargo delivery to the liver.