Figure 7.

Proposed major metabolism pathways of GalNAc₃-conjugated antisense oligonucleotides. Metabolites were detected in rat urine (blue, single asterisk), bile and feces (red, two asterisks), and/or combined (violet, three asterisks). The proposed biotransformation pathway is a result of characterization by LC–MS, including identity of precursor mass, product ions, retention times, and radiometric detection. An in vitro approach using enzymatic incubations was also used to confirm metabolite formation. From the scheme, it is observed that the full mass conjugated parent is rapidly metabolized into predominately oxidized species.