Metabolically Stable Anomeric Linkages Containing GalNAc-siRNA Conjugates: An Interplay among ASGPR, Glycosidase, and RISC Pathways.
Sign Up to like & getrecommendations! Published in 2023 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c01337
Abstract: Conjugation of synthetic triantennary N-acetyl-d-galactosamine (GalNAc) to small interfering RNA (siRNA) mediates binding to the asialoglycoprotein receptor (ASGPR) on the surface of hepatocytes, facilitating liver-specific uptake and siRNA-mediated gene silencing. The natural β-glycosidic bond of… read more here.
Keywords: anomeric linkages; sirna; galnac sirna; glycosidase ... See more keywords
From bench to bedside: Improving the clinical safety of GalNAc–siRNA conjugates using seed-pairing destabilization
Sign Up to like & getrecommendations! Published in 2022 at "Nucleic Acids Research"
DOI: 10.1093/nar/gkac539
Abstract: Abstract Preclinical mechanistic studies have pointed towards RNA interference-mediated off-target effects as a major driver of hepatotoxicity for GalNAc–siRNA conjugates. Here, we demonstrate that a single glycol nucleic acid or 2′–5′-RNA modification can substantially reduce… read more here.
Keywords: safety; seed pairing; sirna conjugates; galnac sirna ... See more keywords
The therapeutic prospects of N-acetylgalactosamine-siRNA conjugates
Sign Up to like & getrecommendations! Published in 2022 at "Frontiers in Pharmacology"
DOI: 10.3389/fphar.2022.1090237
Abstract: RNA interference has become increasingly used for genetic therapy following the rapid development of oligonucleotide drugs. Significant progress has been made in its delivery system and implementation in the treatment of target organs. After a… read more here.
Keywords: prospects acetylgalactosamine; sirna conjugates; sirna; therapeutic prospects ... See more keywords