The beauty of symmetry: siRNA phosphorodithioate modifications reduce stereocomplexity, ease analysis, and can improve in vivo potency

• Main Authors: Sophie Schöllkopf (Author), Stefan Rathjen (Author), Micaela Graglia (Author), Nina Was (Author), Eliot Morrison (Author), Adrien Weingärtner (Author), Lucas Bethge (Author), Judith Hauptmann (Author), Marie Wikström Lindholm (Author)
• Format: Book
• Published: Elsevier, 2024-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Phosphorothioates (PSs) can be essential in stabilizing therapeutic oligonucleotides against enzymatic degradation. However, unless synthesis is performed with stereodefined amidites, each PS introduces a chemically undefined stereocenter, resulting in 2n unique molecules in the final product and af...